Ciliated Epithelium Research Articles

Longitudinal to Transverse Metachronal Wave Transitions in an InVitro Model of Ciliated Bronchial Epithelium.

Myriads of cilia beat on ciliated epithelia, which are ubiquitous in life. When ciliary beats are synchronized, metachronal waves emerge, whose direction of propagation depends on the living system in an unexplained way. We show on a reconstructed human bronchial epithelium invitro that the direction of propagation is determined by the ability of mucus to be transported at the epithelial surface. Numerical simulations show that longitudinal waves maximize the transport of mucus while transverse waves, observed when the mucus is rigid and still, minimize the energy dissipated by the cilia.

Spindle Cells Oncocytoma and Rathke’s Cyst; A Collision Sellar Tumor– Brief Communication & Case Report

Collision tumors comprising of pituitary adenomas with other sellar neoplasms are rare. Histological examination is necessary since preoperative studies cannot guarantee an accurate diagnosis. A 66-year-old man with headache and progressive visual alterations, MRI showed a sellar tumor that was diagnosed as pituitary adenoma and graduated as HV IIIc. He underwent surgery and two lesions were resected, one on the cavernous sinus and the other one in sellar region. The lesion of the venous sinus corresponds to a cyst covered by a ciliated pseudostratified epithelium that was diagnosed as Rathke's cyst, and the second one was formed by a neoplastic lesion of elongated cells with focal cellular atypia in a sarcomatous pattern, forming fascicles alternating with a pattern formed by medium eosinophilic cells predominantly in elongated cells in a stroma with abundant sinusoids. For immunohistochemistry, the epithelium of the cyst was PTTG-1, cytokeratin 6/8, and chromogranin positive, while the other lesion was positive chromogranin, FSH, LH PTTG-1, TTF-1, while the spindle cells area was positive immunoreaction for PTTG-1, GFAP, S-100, and VIM and weak expression for TTF-1. These histologic and immunohistochemical findings are suggestive of spindle cells oncocytoma and Rathke cyst, is a rare sellar collision tumor. The expression of TTF-1 in the spindle cell oncocytoma with the idea of common histogenesis for pituicytoma and SCOs and raise the possibility of more aggressive growth in SCOs as compared to pituicytoma.

O-218 Single-cell RNA sequencing reveals that Ashermańs syndrome is caused by chronic inflammation that induces differential molecular and cellular cartography in the human endometrium

Abstract Study question What is the differential cellular, transcriptomic and immunological differences of the human endometrium in AS versus healthy patients at single cell resolution? Summary answer The epithelial fraction is decreased, the myeloid and lymphoid cell lineages increased with an altered inflammation, inhibition of angiogenesis and EM abnormal remodeling. What is known already Asherman’s Syndrome (AS) is an acquired pathological condition, defined by the presence of intrauterine adhesions (IUAs) causing the uterine walls to adhere to one another resulting in menstrual abnormalities, pelvic pain, infertility, recurrent miscarriage, and abnormal placentation. However, the underlaying cellular, transcriptomic and immunological mechanisms at the single-cell level that occur in AS have not been investigated. Study design, size, duration Single cell RNA-seq (scRNA-seq) was performed on 41,854 cells corresponding to endometrial biopsies from a total of 7 individuals with severe AS (AFS classification 1998). These patients were involved in a phase I/II, prospective, non-randomized, uncontrolled, multicenter, interventional clinical trial authorized by the Spanish Medicines Agency (AEMPS)(2016-003973-23). Control healthy endometrium was represented by 68,026 cell transcriptomes from our previous work (Wang et al. 2020). Participants/materials, setting, methods Seven patients were included. Ultrasound and hysteroscopies were performed in mid secretory phase. Endometrial specimens were digested with collagenase and filtered. Epithelial cells were digested with trypsin and red blood cells removed. After MACS live enrichment, cells were loaded onto ChromiumNext GEM (10xGenomics). Libraries were sequenced in a Novaseq, and reads processed with CellRanger. Quality filtering, normalization, clustering and differential expression analysis were applied from ‘Seurat’ package. Functional enrichment analysis was computed using ‘escape’ package. Main results and the role of chance In total 109,880 cell transcriptomes were compared and found changes in cell population ratios in two specific cell types. First, the epithelial fraction was decreased in AS compared to healthy condition (26.53% vs 45.7%, respectively) specifically the epithelium representing the opening of the window of implantation (WOI) (0.25% vs 2.01%respectively), and the ciliated epithelium (0.84% vs 6.12%, respectively). Second, the myeloid and lymphoid cell lineages, which are much more abundant in AS samples. Macrophages (1.97% vs 0.24%, respectively), CD8+ T cells (3.71% vs 1.34%, respectively), and CD8- T cells (2.28% vs 0.55%, respectively). In addition, there was a different transcriptomic composition represented by three differential linked clusters related to AS condition. First, a unique stromal cluster labelled as stromal_ACTA2 that express genes related to contractile functions (ACTA2, MYH11, DES). Second, a specific AS epithelium cluster closely related to antigen processing and presentation of HLA class II family genes. Third, a KRT8 ACTA2 cluster composed by genes related to collagen (COL3A1 and COL1A1) and IGFBP5. Enrichment analysis performed with ssGSEA revealed the functional impact of the AS condition identifying an increase in different GO terms related to tissue damage, pro-inflammatory processes, inhibition of angiogenesis. Limitations, reasons for caution Despite these promising results, this is an study in progress to be completed with 10 patients Wider implications of the findings These findings describe for the first time the pathophysiology of AS at single cell level with the functional involvement of inflammation, fibrosis, and defective angiogenesis in this pathological condition. Trial registration number Eudra CT 2016-003975-23

Ciliated hepatic foregut cyst: A case report and review of literature.

IntroductionCiliated hepatic foregut cyst (CHFC) is a rare cystic lesion that arises from the embryonic foregut with approximately 100 cases reported. Most commonly identified in segment IV of the liver, CHFC is typically asymptomatic and incidentally found on abdominal imaging. It is important to consider this entity in the differential diagnosis of atypical liver lesions since CHFC carries a risk of transformation into squamous cell carcinoma. A suspicion of CHFC is therefore an indication for surgical resection.Case presentationA 62-year-old male presented to surgery consultation for further evaluation of a hepatic cyst incidentally found on abdominal ultrasound. The patient was completely asymptomatic. Both abdominal computerized tomography and magnetic resonance imaging scan confirmed a 4 cm subcapsular cyst in segment IVa. Additional workup was unremarkable. Considering the diagnostic doubt the patient underwent laparoscopic cyst enucleation. Histology revealed a ciliated pseudostratified epithelium consistent with a CHFC.Clinical discussionCHFC is a rare diagnostic entity that should be considered in the differential diagnosis of cystic hepatic lesions, particularly those located in segment IV of the liver. Since it is frequently asymptomatic, CHFC is usually found incidentally during surgery or imaging studies. Diagnosis of CHFC preoperatively is difficult due to the lack of specific radiographic findings. Moreover, metaplasia and squamous carcinoma can occur. Therefore complete surgical excision is the recommended treatment.ConclusionDespite its rarity, CHFC carries a risk of malignant transformation. Accurate diagnosis is mandatory and surgical excision is recommended even in asymptomatic CHFC.

Interference between avian corona and influenza viruses: The role of the epithelial architecture of the chicken trachea

Respiratory viral infections are among the major causes of disease in poultry. While viral dual infections are known to occur, viral interference in chicken airways is mechanistically hardly understood. The effects of infectious bronchitis virus (IBV) infection on tissue morphology, sialic acid (sia) expression and susceptibility of the chicken trachea for superinfection with IBV or avian influenza virus (AIV) were studied. In vivo, tracheal epithelium of chickens infected with IBV QX showed marked inflammatory cell infiltration and loss of cilia and goblet cells five days post inoculation. Plant lectin staining indicated that sialic acids redistributed from the apical membrane of the ciliated epithelium and the goblet cell cytoplasm to the basement membrane region of the epithelium. After administration of recombinant viral attachment proteins to slides of infected tissue, retained binding of AIV hemagglutinin, absence of binding of the receptor binding domain (RBD) of IBV M41 and partial reduction of IBV QX RBD were observed. Adult chicken trachea rings were used as ex vivo model to study the effects of IBV QX-induced pathological changes and receptor redistribution on secondary viral infection. AIV H9N2 infection after primary IBV infection was delayed; however, final viral loads reached similar levels as in previously uninfected trachea rings. In contrast, IBV M41 superinfection resulted in 1000-fold lower viral titers over the course of 48 h. In conclusion, epithelial changes in the chicken trachea after viral infection coincide with redistribution and likely specific downregulation of viral receptors, with the extend of subsequent viral interference dependent on viral species.

Dmrt2 and myf5 Link Early Somitogenesis to Left-Right Axis Determination in Xenopus laevis.

The vertebrate left-right axis is specified during neurulation by events occurring in a transient ciliated epithelium termed left-right organizer (LRO), which is made up of two distinct cell types. In the axial midline, central LRO (cLRO) cells project motile monocilia and generate a leftward fluid flow, which represents the mechanism of symmetry breakage. This directional fluid flow is perceived by laterally positioned sensory LRO (sLRO) cells, which harbor non-motile cilia. In sLRO cells on the left side, flow-induced signaling triggers post-transcriptional repression of the multi-pathway antagonist dand5. Subsequently, the co-expressed Tgf-β growth factor Nodal1 is released from Dand5-mediated repression to induce left-sided gene expression. Interestingly, Xenopus sLRO cells have somitic fate, suggesting a connection between LR determination and somitogenesis. Here, we show that doublesex and mab3-related transcription factor 2 (Dmrt2), known to be involved in vertebrate somitogenesis, is required for LRO ciliogenesis and sLRO specification. In dmrt2 morphants, misexpression of the myogenic transcription factors tbx6 and myf5 at early gastrula stages preceded the misspecification of sLRO cells at neurula stages. myf5 morphant tadpoles also showed LR defects due to a failure of sLRO development. The gain of myf5 function reintroduced sLRO cells in dmrt2 morphants, demonstrating that paraxial patterning and somitogenesis are functionally linked to LR axis formation in Xenopus.

Baclofen (fun drug) and ethanol combined poisoning in humans: A histopathology and morphometry model

Background– This study intends to address the scarcity of data regarding the pathogenesis of Baclofen poisoning in humans, which has seen a recent increase, worldwide, especially amongst the young people. Another reason for the conduction of this study was lack of the substantial data about the histo-pathological findings of lungs, in synergistic toxicity of Baclofen with Ethanol, in-spite of it being very common in humans, and both being respiratory depressant with similar mechanism of action. Purpose– The authors aimed to understand the pathogenesis of fatal poisonings in humans due to Baclofen in combination with Ethanol via an animal research model. The enhancement of the overall scientific literature by extending research along the lines of the handful studies available in this regard was another adjunct goal of the study. Material and methodsFifteen Wistar rats were divided into control and test group of five and ten subjects respectively. The test group was further divided into two sub-groups of five each, with Baclofen administered to one, and it in conjunction with Ethanol to the other, in lowest dosages adjusted for the humans. Rats in both the groups were euthanized by dislocation of the cervical vertebrae for the histopathology examination. ResultsCapillary and venous plethora, hemorrhages in the inter-alveolar septi, hemorrhages into the alveoli and sludging was seen in the 1st sub-group. The plethora of venules, capillaries and arterioles, with sludging by the WBC (white blood corpuscle) infiltrates was seen in the 2nd sub-group. Desquamation of the ciliated epithelium and edematous thickening of the intra-alveolar septi, along with features suggestive of the peri-vascular edema was seen in the 2nd sub-group. The morphometric analysis of the micro vessels showed a significantly higher value of the arteriolar diameter in the 2nd sub-group, in comparison to 1st, but the venular diameter in the two sub-groups did not differ to any extent.

Post-hatch changes in the histological structure of the oviduct and associated 17β-estradiol profiles in guinea hens (Numida meleagris)

There are limited data available on the biology of guinea fowls. The objective of this study was to document post-hatch histological and stereological changes in the oviducts of 56 guinea hens and associated 17β-estradiol profiles until 32 weeks of age and to explore changes in the oviducal mucosal fold as an index of oviducal growth. Mucosal folds in all regions of the oviduct increased significantly ( P < 0.0001) from 4 to 28 weeks of age. Concentrations of plasma 17β-estradiol increased from 20 to 28 weeks of age, when it stabilized. Mucosal folds in the oviducts of sexually active hens were highest in the uterine region and lowest in the infundibular lip. Intercorrelations among 17β-estradiol concentration, height of mucosal folds, and oviducal weight were strong and positive in these birds. Most of the oviduct epithelium consisted of pseudostratified columnar ciliated epithelium. Both the height of oviducal folds and peripheral estradiol concentrations increased significantly from 20 to 28 weeks of age, which confirms the role of estradiol in oviducal growth in the avian species. The height of oviducal mucosal folds appears to be a good measure of oviducal growth.

Viral cytopathic effect in maxillary sinus epithelium and SARS-CoV-2: Pitfalls in diagnostic characterization

Viral cytopathic effects (VCE) are a well-known phenomenon associated with SARS-CoV-2 infection, especially in the cells associated with the lungs. Because maxillary sinus epithelium expresses angiotensin-converting enzyme 2, cells associated with it are more likely to become infected with SARS-CoV-2 and develop VCE. If VCE is seen in with background of a confirmatory COVID-19 diagnosis, then connecting both become quite convincing. However, the diagnostic problem is expected when a similar VCE is seen without any confirmatory diagnosis of CODIV-19. We reported a biopsy sample of maxillary sinusitis in a COVID-19 negative patient. Histopathological examination revealed a pathognomonic VCE in the localized proliferating pseudostratified ciliated epithelium. The only confirmatory aspect linking this VCE with the SARS-CoV-2 was the detection of virus particles at the tissue level. In the present paper, pitfalls and recommendations for future research on this topic are discussed.

Clinico-haemato-biochemical and Pathological Alteration of Pyometra in Canines

Background: Pyometra is a pathological state of the compromised uterus of grown-up to old, diestrum bitches. Pyometra is easy to identify but can be more challenging when there is no vaginal discharge. In the present study, an attempt was made to find out the pathogen involvement and clinico-haemato-biochemical alteration in bitches affected with Pyometra. Methods: Twelve bitches with a history of inappetence, polydipsia, dirty vaginal discharge, occasional vomition irrespective of breeds and age groups were clinically examined and diagnosed as pyometra. The presumptive clinical diagnosis was based on case history, clinical signs, vaginal cytology, abdominal ultrasonography or radiography, gross examination of a pus-filled uterus after the ovariohysterectomy. Result: Vaginal examination revealed brown chocolate malodorous vaginal discharge with discolouration of the perivulval tissue. Abdominal ultrasound showed hyperplasia with echogenic material in the uterine wall along with distended uterine horns containing a large volume of cellular contents. Radiographic imaging revealed cranio-dorsal displacement of the small intestine and a twisted uniform tubular opacity with a distended uterus. The vaginal cytology revealed a large number of degenerated neutrophils, intermediate and parabasal cells. Escherichia coli were the major pathogen isolated from the pyometra uteri of bitches. The surface of the endometrium was columnar ciliated epithelium, with hyperplasia of subepithelial tissue and thick muscularis. The haemato-biochemical evaluation in pyometra infected bitches revealed decreased haemoglobin (Hb), packed cell volume (PCV), total erythrocytic count (TEC) and lymphocyte count indicating the microcytic hypochromic type of anaemia. Leucocytosis with a predominant absolute neutrophilia and lymphocytosis were consistently found in canine pyometra. There was a significantly elevated profile of blood urea nitrogen, creatinine, transaminases and alkaline phosphatase as well as total proteins observed in pyometric female dogs as compared to healthy ones which may have diagnostic and prognostic importance, which also indicated damage of vital organ caused by bacterial endotoxins. The haemato-biochemical indices correlating with imaging techniques, vaginal cytology and histopathological examination can serve as good prognostic markers in bitches with pyometra.

SARS-CoV-2 Infection Dysregulates Cilia and Basal Cell Homeostasis in the Respiratory Epithelium of Hamsters.

Similar to many other respiratory viruses, SARS-CoV-2 targets the ciliated cells of the respiratory epithelium and compromises mucociliary clearance, thereby facilitating spread to the lungs and paving the way for secondary infections. A detailed understanding of mechanism involved in ciliary loss and subsequent regeneration is crucial to assess the possible long-term consequences of COVID-19. The aim of this study was to characterize the sequence of histological and ultrastructural changes observed in the ciliated epithelium during and after SARS-CoV-2 infection in the golden Syrian hamster model. We show that acute infection induces a severe, transient loss of cilia, which is, at least in part, caused by cilia internalization. Internalized cilia colocalize with membrane invaginations, facilitating virus entry into the cell. Infection also results in a progressive decline in cells expressing the regulator of ciliogenesis FOXJ1, which persists beyond virus clearance and the termination of inflammatory changes. Ciliary loss triggers the mobilization of p73+ and CK14+ basal cells, which ceases after regeneration of the cilia. Although ciliation is restored after two weeks despite the lack of FOXJ1, an increased frequency of cilia with ultrastructural alterations indicative of secondary ciliary dyskinesia is observed. In summary, the work provides new insights into SARS-CoV-2 pathogenesis and expands our understanding of virally induced damage to defense mechanisms in the conducting airways.

Respiratory epithelial adenomatoid hamartoma - A neglected entity in the nasal cavity

Abstract Respiratory epithelial adenomatoid hamartoma (REAH) is a rare subtype of hamartoma which consist of the proliferation of glandular spaces and is lined by ciliated epithelium or goblet cells. Here, we report the case of REAH in a 45-year-old male who presented with bilateral nasal blockage in the past 1 year. The bilateral polypoidal nasal mass was excised. Microscopically, the proliferation of glandular spaces lined by ciliated epithelium and goblet cells and thickened eosinophilic basement membrane was seen. Immunohistochemistry showed positivity for pancytokeratin. One should always consider REAH as one of the differential diagnoses of a symptomatic polypoidal sinonasal mass.

Analysis of mucociliary transport of the maxillary sinus mucosa after surgical trauma and in the presence of chronic inflammation

Background: The membrane of the maxillary sinus actively participates in the protective function of the upper respiratory tract through the mucociliary transport carried out by its ciliated epithelium. The presence of pathological changes in the sinus cavity directly affects the ability of the Schneider’s membrane to effectively perform its drainage function. The activity of mucociliary transport is reduced and the time required for the cleansing activity of the maxillary sinus is increased. Methods: In the study we are introducing, a total of 20 patients were included, divided into two groups. Patients were scheduled for local maxillary sinus plastic surgeries. Group 1 included patients in whom we did not find a change in the thickness of the mucosa of the maxillary sinus on CBCT. In group two we selected patients with radiological data for thickened mucosa of the maxillary sinus between 5 mm and 7 mm. Before closing the communication, we placed a saccharin granule in the maxillary sinus. We assessed the activity of mucociliary transport by measuring the time for which patients registered a sweet taste in their mouth. Results: In all of the 20 patients, we found prolonged drainage function of the maxillary sinus mucosa. For group 1, this time was recorded in the interval from 115 minutes to 238 minutes (average 137 minutes). In group 2, the time reported was between 210 and 345 minutes (average value 270.75 minutes). Conclusions: Based on the results obtained, we can conclude that surgical trauma and chronic inflammation of the membrane of the maxillary sinus affect the efficiency of the mucociliary transport.

ASSESSMENT OF LOCAL MUCOCILIARY CLEARANCE OF THE MIDDLE NASAL MEATUS AFTER DIFFERENT TYPES OF SURGICAL ACCESS TO THE MAXILLARY SINUS

Abstract. The paper considers an original method for asessment the ciliar beating frequency (CBF) of the ciliated epithelium (mucociliary clearance) of the nasal mucosa using modern high-speed digital video recording of the microscopic picture of the brushed specimen, which followed by mathematical processing. This method used to study the local mucociliary clearance of the middle nasal meatus, which plays a key role in the modern understanding of the osteomeatal complex function. The normal values of the CBF of the middle nasal meatus in healthy individuals (11.76 ± 3.01 Hz) were determined. We studied the changes in the CBF of the ciliary epithelium of the middle nasal meatus with foreign bodies of the maxillary sinus. A correlation found between changes in the CBF of the ciliary epithelium of the middle nasal meatus and the CT changes in the region of the middle nasal meatus and paranasal sinuses. This also determined the effect of surgical trauma on the CBF of the middle nasal meatus and its changes in the early (up to 1 month) and late (1-6 months) following period. We clearly proved the dependence of the mucociliary clearance of the middle nasal meatus on the type of surgical access to the maxillary sinus during surgical interventions for foreign bodies of the maxillary sinus. We revealed certain advantages of transmaxillary and prelacrimal surgical access to the maxillary sinus over endonasal antrostomy during surgical interventions for foreign bodies of the maxillary sinus. Our data allow optimizing surgical interventions on the maxillary sinus with minimization of surgical trauma to the ciliary epithelium of the middle nasal passage and improving the functional and morphological results of surgical treatment of foreign bodies in the maxillary sinuses.

Host\u2013pathogen dynamics in longitudinal clinical specimens from patients with COVID-19

Rapid dissemination of SARS-CoV-2 sequencing data to public repositories has enabled widespread study of viral genomes, but studies of longitudinal specimens from infected persons are relatively limited. Analysis of longitudinal specimens enables understanding of how host immune pressures drive viral evolution in vivo. Here we performed sequencing of 49 longitudinal SARS-CoV-2-positive samples from 20 patients in Washington State collected between March and September of 2020. Viral loads declined over time with an average increase in RT-QPCR cycle threshold of 0.87 per day. We found that there was negligible change in SARS-CoV-2 consensus sequences over time, but identified a number of nonsynonymous variants at low frequencies across the genome. We observed enrichment for a relatively small number of these variants, all of which are now seen in consensus genomes across the globe at low prevalence. In one patient, we saw rapid emergence of various low-level deletion variants at the N-terminal domain of the spike glycoprotein, some of which have previously been shown to be associated with reduced neutralization potency from sera. In a subset of samples that were sequenced using metagenomic methods, differential gene expression analysis showed a downregulation of cytoskeletal genes that was consistent with a loss of ciliated epithelium during infection and recovery. We also identified co-occurrence of bacterial species in samples from multiple hospitalized individuals. These results demonstrate that the intrahost genetic composition of SARS-CoV-2 is dynamic during the course of COVID-19, and highlight the need for continued surveillance and deep sequencing of minor variants.

Gross Morphological and Histological Features of Larynx in Yankasa Sheep ‎‎(Ovis aries)‎

The present study, conducted on the larynx of five adult Yankasa sheep of local breed, aimed at exploring its basic anatomy and histological features. The larynx consists of four cartilages; the unpaired epiglottis rostroventral, unpaired thyroid ventrally, dorsal paired arytenoid, and caudal unpaired cricoid. These cartilages presented distinct morphological features and were connected to each other by ligaments. The intrinsic laryngeal muscles include; the dorsal cricoarytenoid and transverse arytenoid muscles. The lateral cricoarytenoid was concealed by the thyroid laminae. The ventrally located thyroarytenoid and cricothyroid muscles. The laryngeal cavity comprised of rostral vestibule, a narrow middle glottic cleft and a wide infraglottic cavity caudally. Histologically, the epiglottis was lined by stratified squamous keratinized epithelium, the thyroid cartilage was lined by pseudostratified columnar epithelium, whereas the arytenoid cartilage was lined by pseudostratified columnar ciliated epithelium with goblet cells. The loose irregular loose connective tissue of the propria submucosa comprised of connective tissue cells mainly fibroblast, and fine blood capillaries, whereas the deeper part presented glandular tissues, ducts, fat cells and cartilages. It is envisaged that the study has provided basic information on gross and histological feature of the larynx in the Yankasa sheep.

Odontogenic foreign bodies of the maxillary sinus

The anatomical proximity of the roots of molars and premolars to the floor of the maxillary sinus creates the risk for the formation of odontogenic sinusitis, which is often initiated by foreign bodies entering the sinus during dental procedures. Odontegenic foreign bodies (FB) of the maxillary sinus are usually represented by fragments of tooth roots, filling material, plastic material used in sinus lifting, dental implants, dental burs, pins and needles. FB causes the development of an inflammatory process in the sinus due to the penetration of highly virulent microbiota of the oral cavity or the formation of a fungal body. In rare cases, small FB can be evacuated into the nasal cavity as a result of the movement of the cilia of the ciliated epithelium. Most odontogenic FB are radiopaque and are detected by computed tomography (CT) of the paranasal sinuses. CT data allows to accurately localize FB and choose a treatment tactics.

DYNAMIC CHANGES OF TISSUE ENZYMES AND THE ITS INFLUENCE ON WOUND HEALING OF NASAL MUCOSA IN THE POSTOPERATIVE PERIOD

Intranasal surgery is widely spread all over the world and has the leading position among all otorhinolaryngological surgical interventions. However, any surgery makes sensitive trauma to the ciliaryepithelium that covers the nasal cavity and paranasal sinuses despite the modern technics of operations. That’s why reveling peculiarities, patterns and ways of correction of nasal mucosa regeneration in the postoperative period is very important for clinicians. So the main aim of our paper is to investigate the role of some tissue enzymes in the process of nasal mucosa regeneration after surgical interventions on the structures of the nasal cavity in adults. As a result of our investigation, the role of some tissue enzymes was shown. We have based the usage of drugs that influence wound healing. Thus, the proper medicines have positive effects on the regeneration processes of the ciliated epithelium. A more thorough investigation of the role of these enzymes will allow developing methods of its correction for improving the efficiency of endonasal surgery rapid and qualitative recovery of mucociliary clearance.

Regional Differences in Mucociliary Clearance in the Upper and Lower Airways.

As the nasal cavity is the portal of entry for inspired air in mammals, this region is exposed to the highest concentration of inhaled particulate matter and pathogens, which must be removed to keep the lower airways sterile. Thus, one might expect vigorous removal of these substances via mucociliary clearance (MCC) in this region. We have investigated the rate of MCC in the murine nasal cavity compared to the more distal airways (trachea). The rate of MCC in the nasal cavity (posterior nasopharynx, PNP) was ∼3–4× greater than on the tracheal wall. This appeared to be due to a more abundant population of ciliated cells in the nasal cavity (∼80%) compared to the more sparsely ciliated trachea (∼40%). Interestingly, the tracheal ventral wall exhibited a significantly lower rate of MCC than the tracheal posterior membrane. The trachealis muscle underlying the ciliated epithelium on the posterior membrane appeared to control the surface architecture and likely in part the rate of MCC in this tracheal region. In one of our mouse models (Bpifb1 KO) exhibiting a 3-fold increase in MUC5B protein in lavage fluid, MCC particle transport on the tracheal walls was severely compromised, yet normal MCC occurred on the tracheal posterior membrane. While a blanket of mucus covered the surface of both the PNP and trachea, this mucus appeared to be transported as a blanket by MCC only in the PNP. In contrast, particles appeared to be transported as discrete patches or streams of mucus in the trachea. In addition, particle transport in the PNP was fairly linear, in contrast transport of particles in the trachea often followed a more non-linear route. The thick, viscoelastic mucus blanket that covered the PNP, which exhibited ∼10-fold greater mass of mucus than did the blanket covering the surface of the trachea, could be transported over large areas completely devoid of cells (made by a breach in the epithelial layer). In contrast, particles could not be transported over even a small epithelial breach in the trachea. The thick mucus blanket in the PNP likely aids in particle transport over the non-ciliated olfactory cells in the nasal cavity and likely contributes to humidification and more efficient particle trapping in this upper airway region.

Bordetella pertussis-infected innate immune cells drive the anti-pertussis response of human airway epithelium

Pertussis is a severe respiratory tract infection caused by Bordetella pertussis. This bacterium infects the ciliated epithelium of the human airways. We investigated the epithelial cell response to B. pertussis infection in primary human airway epithelium (HAE) differentiated at air–liquid interface. Infection of the HAE cells mimicked several hallmarks of B. pertussis infection such as reduced epithelial barrier integrity and abrogation of mucociliary transport. Our data suggests mild immunological activation of HAE by B. pertussis indicated by secretion of IL-6 and CXCL8 and the enrichment of genes involved in bacterial recognition and innate immune processes. We identified IL-1β and IFNγ, present in conditioned media derived from B. pertussis-infected macrophage and NK cells, as essential immunological factors for inducing robust chemokine secretion by HAE in response to B. pertussis. In transwell migration assays, the chemokine-containing supernatants derived from this HAE induced monocyte migration. Our data suggests that the airway epithelium on its own has a limited immunological response to B. pertussis and that for a broad immune response communication with local innate immune cells is necessary. This highlights the importance of intercellular communication in the defense against B. pertussis infection and may assist in the rational design of improved pertussis vaccines.