Inflammatory Cellular Components Research Articles

The Morphology of Nasal Polyps in Different Age Groups: Histopathological Features.

Nasal polyps (NPs) represent the end-stage manifestation of chronic rhinosinusitis (CRS), a relatively common pathological condition encountered in all ages of life. The aim of our study was to evaluate the histological features and inflammatory cellular components of NPs in a retrospective cohort (143 cases) of pediatric, adult and elderly populations in order to discuss the possible morphological age-related differences statistically documented. In the pediatric group, the inflammatory infiltrate presented many eosinophils mixed with lymphocytes, while in the adult population, lymphocytes and plasma cells were mainly evident, frequently with a perivascular distribution or with the formation of subepithelial lymphoid nodules. In the elderly population, inflammation was less evident and was associated with cavernous-like angecthatic structures with thrombotic stratification. Nearly all morphological findings exhibited statistically significant values among differently aged subgroups. Our results support the presence of histological specificities of NPs at different ages of life, providing new insight into the etiopathogenesis of NPs. The future role of biological therapies, mainly in cases refractory to already available standard medical and surgical treatments, may be analyzed by a prospective study using a larger cohort with a long-term evaluation also in relation to a possible relapse.

A deep transfer learning framework for the automated assessment of corneal inflammation on in vivo confocal microscopy images.

PurposeInfiltration of activated dendritic cells and inflammatory cells in cornea represents an important marker for defining corneal inflammation. Deep transfer learning has presented a promising potential and is gaining more importance in computer assisted diagnosis. This study aimed to develop deep transfer learning models for automatic detection of activated dendritic cells and inflammatory cells using in vivo confocal microscopy images.MethodsA total of 3453 images was used to train the models. External validation was performed on an independent test set of 558 images. A ground-truth label was assigned to each image by a panel of cornea specialists. We constructed a deep transfer learning network that consisted of a pre-trained network and an adaptation layer. In this work, five pre-trained networks were considered, namely VGG-16, ResNet-101, Inception V3, Xception, and Inception-ResNet V2. The performance of each transfer network was evaluated by calculating the area under the curve (AUC) of receiver operating characteristic, accuracy, sensitivity, specificity, and G mean.ResultsThe best performance was achieved by Inception-ResNet V2 transfer model. In the validation set, the best transfer system achieved an AUC of 0.9646 (P<0.001) in identifying activated dendritic cells (accuracy, 0.9319; sensitivity, 0.8171; specificity, 0.9517; and G mean, 0.8872), and 0.9901 (P<0.001) in identifying inflammatory cells (accuracy, 0.9767; sensitivity, 0.9174; specificity, 0.9931; and G mean, 0.9545).ConclusionsThe deep transfer learning models provide a completely automated analysis of corneal inflammatory cellular components with high accuracy. The implementation of such models would greatly benefit the management of corneal diseases and reduce workloads for ophthalmologists.

Current concepts in atherosclerosis

Atherosclerosis is a complex disease process. It is increasingly recognised that both lipoprotein retention and inflammatory cellular components are intricately related in the initiation and development of atherosclerotic plaque. LDL-c (cholesterol) has been long established as a cause for atherosclerosis; additionally, inflammatory cells such as monocytes and subsequently foam cells have also been directly linked to the progression of atherosclerotic disease. Emerging data suggest that structures outside vascular intima and media are also closely related to atherosclerosis. Perivascular adipose tissue (PVAT) may be a determinant of the inflammatory status of the atherosclerotic plaque. All these features are becoming extremely relevant as therapies against atherosclerosis are targeting both lipid retention and inflammation. Recently, there has been some success in these novel therapies, such as the proprotein convertase subtilisin-kexin type 9 (PCSK-9) inhibitor evolocumab and the interleukin-1ß neutralising antibody, canakinumab, in reducing cardiovascular events when added to standard therapy such as statin. This review will discuss the pathogenesis of atherosclerosis, including some novel features, and its management using new anti-atherosclerotic drugs.

Chemopreventive Strategies for Inflammation-Related Carcinogenesis: Current Status and Future Direction.

A sustained and chronically-inflamed environment is characterized by the presence of heterogeneous inflammatory cellular components, including neutrophils, macrophages, lymphocytes and fibroblasts. These infiltrated cells produce growth stimulating mediators (inflammatory cytokines and growth factors), chemotactic factors (chemokines) and genotoxic substances (reactive oxygen species and nitrogen oxide) and induce DNA damage and methylation. Therefore, chronic inflammation serves as an intrinsic niche for carcinogenesis and tumor progression. In this article, we summarize the up-to-date findings regarding definitive/possible causes and mechanisms of inflammation-related carcinogenesis derived from experimental and clinical studies. We also propose 10 strategies, as well as candidate agents for the prevention of inflammation-related carcinogenesis.

Significance of NF-κB activation in immortalization of nasopharyngeal epithelial cells.

NF-κB is a key regulator of inflammatory response and is frequently activated in human cancer including the undifferentiated nasopharyngeal carcinoma (NPC), which is common in Southern China including Hong Kong. Activation of NF-κB is common in NPC and may contribute to NPC development. The role of NF-κB activation in immortalization of nasopharyngeal epithelial (NPE) cells, which may represent an early event in NPC pathogenesis, is unknown. Examination of NF-κB activation in immortalization of NPE cells is of particular interest as the site of NPC is often heavily infiltrated with inflammatory cellular components. We found that constitutive activation of NF-κB signaling is a common phenotype in telomerase-immortalized NPE cell lines. Our results suggest that NF-κB activation promotes the growth of telomerase-immortalized NPE cells, and suppression of NF-κB activity inhibits their proliferation. Furthermore, we observed upregulation of c-Myc, IL-6 and Bmi-1 in our immortalized NPE cells. Inhibition of NF-κB downregulated expression of c-Myc, IL-6 and Bmi-1, suggesting that they are downstream events of NF-κB activation in immortalized NPE cells. We further delineated that EGFR/MEK/ERK/IKK/mTORC1 is the key upstream pathway of NF-κB activation in immortalized NPE cells. Elucidation of events underlying immortalization of NPE cells may provide insights into early events in pathogenesis of NPC. The identification of NF-κB activation and elucidation of its activation mechanism in immortalized NPE cells may reveal novel therapeutic targets for treatment and prevention of NPC.

Solid form of epithelioid hemangioma: a case report.

Epithelioid hemangioma (EH) is an uncommon benign vascular tumor, of controversial etiology that usually presents as a slowly growing nodule on the face or digit of a middle-aged woman. 1 Most lesions have a nonspecific nodular appearance with frequent secondary changes such as excoriation and bleeding. Multiplicity is also a common finding. Histopathologically, EH is characterized by a mixture of vascular proliferation and marked mixed inflammatory cell infiltration, and was first de scribed by Wells and Whimster 2 as angiolymphoid hyperplasia with eosinophilia. The proliferation of vascular structures lined with prominent endothelial cells is a distinguishing feature of EH. The epithelioid endothelial cells that protrude into the vascular lumen create a characteristic “cobble-stone” or “tombstone” appearance. A chronic inflammatory cell infiltration in cluding lymphoplasma cells and eosinophils is a consistent find ing. EH has a diverse range of microscopic features, depending on the composition and distribution of the vascular and inflam matory cellular components. EH has been described in the literature as an inflammatory angiomatous nodule or, an atypical or pseudopyogenic granuloma, 3,4 when infiltration of various inflammatory cells is predominant, and a histiocytoid hemangi oma 5 when cobble stone-like endothelial cells are conspicuous. Some cases of EH consist entirely of solid sheets of epithelioid to spindled cells without fully canalized vascular structures. The solid form of EH can be difficult to diagnose and is occa sionally misdiagnosed as a malignant vascular tumor. EH is a benign neoplasm and surgical excision is sufficient for its treat ment. Recently, we experienced a solid form of EH with no inflammatory component, which showed a dramatic change into the typical morphology on the consecutive biopsy. This is the first reported Korean case of a solid form of EH, which patholo gists should include in the differential diagnosis of epithelioid vascular lesions to avoid overdiagnosis of epithelioid vascular malignancies.

Histopathological and ultrastructural studies on human cutaneous leishmaniasis

Leishmania, a genus of intracellular protozoan parasites of macrophages, is the etiologic agent of cutaneous and visceral disease in man. In our study, localized cutaneous infections with leishmania were studied by light and transmission electron microscopy in 16 patients at phases ranging from onset to a progressive disease. In early infections, epidermal changes could be detected as deep hemorrhagic ulcer characterized by focal massive necrosis of the epidermal layers. Spongiotic vesicles in the epidermis were prominent containing the amastigotes. The dermal changes appeared in the form of diffuse inflammatory infiltrate predominantly composed of macrophages, epithelioid cells, lymphocytes, mast cells, and few plasma cells and eosinophils. Macrophages laden with the parasites were seen dissociating the striated muscle and the collagen bundles which showed degenerative and necrotic changes. In late stages of the disease, multiple granulomas formed predominantly of macrophages containing promastigotes and amastigotes, giant cells, epithelioid cells, and some mast cells were seen in the dermis. Some macrophages appeared vacuolated and loaded with the parasite. The dermal vasculature showed congestion, swelling of the endothelial cells, and fibrinoid necrosis of the wall. Some congested blood vessels demonstrated margination and diapedesis of inflammatory cells. By transmission electron microscopy, intact and degenerated amastigotes were seen phagocytosed inside the macrophagal parasitophorus vacuoles. Erythrophagocytosis and the reaction of other inflammatory cellular components were also described. These results clarified the lesions of leishmania invasion into the skin of the affected patients and its defensive mechanism. Moreover, the host macrophagal–parasite relationship was shown on ultrastructural level.

Histopathological, histochemical and immunohistochemical findings of the small intestine in goats naturally infected by Trichostrongylus colubriformis

Gastrointestinal (GI) strongyle infection remains one of the main constraints to goat production worldwide. Samples of small intestine from 15 Syrian goats naturally infected with Trichostrongylus colubriformis were examined by routine histology, histochemistry and immunohistochemistry to describe the histological changes and the phenotypes of inflammatory cellular components of the mucosa. Results indicated that the immune response to infection by T. colubriformis was characterized by an increased rate of the severity of the histologic lesions, an increase rate of T cell lymphocytes recruitment to the intestinal mucosa and quantitative and qualitative changes in the histochemical composition of mucin in goblet cells.

A microfluidics approach towards high-throughput pathogen removal from blood using margination.

Sepsis is an adverse systemic inflammatory response caused by microbial infection in blood. This paper reports a simple microfluidic approach for intrinsic, non-specific removal of both microbes and inflammatory cellular components (platelets and leukocytes) from whole blood, inspired by the invivo phenomenon of leukocyte margination. As blood flows through a narrow microchannel (20 × 20 µm), deformable red blood cells (RBCs) migrate axially to the channel centre, resulting in margination of other cell types (bacteria, platelets, and leukocytes) towards the channel sides. By using a simple cascaded channel design, the blood samples undergo a 2-stage bacteria removal in a single pass through the device, thereby allowing higher bacterial removal efficiency. As an application for sepsis treatment, we demonstrated separation of Escherichia coli and Saccharomyces cerevisiae spiked into whole blood, achieving high removal efficiencies of ∼80% and ∼90%, respectively. Inflammatory cellular components were also depleted by >80% in the filtered blood samples which could help to modulate the host inflammatory response and potentially serve as a blood cleansing method for sepsis treatment. The developed technique offers significant advantages including high throughput (∼1 ml/h per channel) and label-free separation which allows non-specific removal of any blood-borne pathogens (bacteria and fungi). The continuous processing and collection mode could potentially enable the return of filtered blood back to the patient directly, similar to a simple and complete dialysis circuit setup. Lastly, we designed and tested a larger filtration device consisting of 6 channels in parallel (∼6 ml/h) and obtained similar filtration performances. Further multiplexing is possible by increasing channel parallelization or device stacking to achieve higher throughput comparable to convectional blood dialysis systems used in clinical settings.

Increased apoptosis of CD4 and CD8 T lymphocytes in the airways of horses with recurrent airway obstruction

Recurrent airway obstruction (RAO, also known as equine heaves) is an inflammatory condition similar to human asthma caused by exposure of susceptible horses to poorly ventilated stable environments. The disease is characterized by neutrophilic airway inflammation, mucus hypersecretion and reversible bronchoconstriction. This inflammatory process is mediated by several factors, including antibodies, cytokines, resident cells of the airway and inflammatory cellular components that arrive in the respiratory tract. An increasing body of evidence has lent support to the concept that a dysregulation of T cell apoptosis may play a central role in the development of airway inflammation and the associated asthma. Therefore, the aim of this study was to investigate early and late apoptosis of CD4 and CD8 T cell subpopulations obtained from the airways of acute RAO-positive animals after exposure to hay/straw. The percentages of CD4 and CD8 T cells and their associated frequencies of apoptosis were quantified using flow cytometry. Hay/straw exposure induced clinical airway obstruction, airway neutrophilia and increased airway mucus production in RAO-positive horses. In addition, allergen exposure increased the percentage of CD4 T cells in RAO-positive horses as well as the frequency of early and late apoptosis in both CD4 and CD8 lymphocyte subpopulations. These results suggest that the higher frequency of lymphocyte apoptosis may play a role in disease progression of horses afflicted with RAO and may partially explain the characteristic remission of this pathological condition once the allergen source is removed. However, further studies are needed to clarify the role of T cell apoptosis in RAO-affected horses.

Therapeutic implications of chemokine-mediated pathways in atherosclerosis: realistic perspectives and utopias

Current perspectives on the pathogenesis of atherosclerosis strongly support the involvement of inflammatory mediators in the establishment and progression of atherosclerostic lesions. Chemokine-mediated mechanisms are potent regulators of such processes by orchestrating the interactions of inflammatory cellular components of the peripheral blood with cellular components of the arterial wall. The increasing evidence supporting the role of chemokine pathways in atherosclerosis renders chemokine ligands and their receptors potential therapeutic targets. In the following review, we aim to highlight the special structural and functional features of chemokines and their receptors in respect to their roles in atherosclerosis, and examine to what extent available data can be applied in disease management practices.

Chemokines in vascular pathology (Review)

Clinical complications of atherosclerosis are major causes of morbidity and mortality in Western societies. Recent evidence suggests that formation of atherosclerotic lesions is an inflammatory process involving multiple molecular pathways. Chemokine-mediated mechanisms are potent regulators of such processes by orchestrating the interactions of inflammatory cellular components of the peripheral blood with cellular components of the arterial wall. The increasing evidence supporting the role of chemokine-pathways in atherosclerosis renders chemokine ligands and their receptors potential therapeutic targets. In the following review, we intend to highlight the special structural and functional features of each chemokine sub-family in respect to their role in atherosclerosis and discuss to what extent such knowledge could be applied in diagnostic, prognostic or therapeutic practices.

The eosinophil as a therapeutic target in asthma: beginning of the end, or end of the beginning?

A major goal in asthma therapy is to reduce or prevent the inflammatory response associated with bronchial hyperresponsiveness, reversible airway obstruction and airway remodelling. However, because of the complex nature of the disease, a single target for such an ideal therapeutic approach remains elusive. To ensure a more rational design of anti-asthma drugs, recent investigations have attempted to elucidate the roles of inflammatory cellular components in asthma. Such studies have shown that eosinophilic infiltration is a prominent feature in the pathophysiology of asthma. Nonetheless, the role of the eosinophil in asthma has been questioned following recent human studies investigating the efficacy of a novel therapeutic strategy targeted at eosinophils.

Immunohistochemical analysis of experimental autoimmune uveoretinitis (EAU) induced by interphotoreceptor retinoid-binding protein (IRBP) in the rat.

Experimental autoimmune uveoretinitis (EAU) was induced in rats by immunization with bovine interphotoreceptor retinoid-binding protein (IRBP) and studied by immunohistochemistry. In general, the IRBP induction of inflammatory cellular components and expression of immune-related antigens on various non-lymphoid cells resembled those provoked by S-antigen (S-Ag). However, differences were found between the two diseases, including: 1) The increase in T suppressor/cytotoxic cells occurred in IRBP EAU more rapidly than in S-Ag EAU. 2) Fewer numbers of non-lymphoid cells expressed major histocompatibility complex class II surface antigens in IRBP EAU than in S-Ag EAU. The immunopathogenic mechanism of EAU induced by these two retinal antigens are discussed.