Higher Numbers Of Inflammatory Cells Research Articles

New miRNA classifier distinguishes CTCL from benign skin disorders

Cutaneous T-cell lymphomas (CTCL) are the most frequently occurring primary skin lymphoma. These skin lesions contain a high number of inflammatory cells but early diagnosis of CTCL is challenging because of its clinical, pathological and histological similarity to benign inflammatory skin lesions such as psoriasis and eczema. Now, a study has shown that a microRNA (miRNA) classifier can distinguish CTCL from benign skin disorders. Senior researcher Niels Odum explains the background to the study “we decided to address if a novel miRNA technology could help solve a 100-year-old problem—namely, how to distinguish cutaneous CTCL from benign dermatosis”.

Effect of inhaled corticosteroids on small airway inflammation in patients with bronchial asthma

Bronchial asthma is a chronic inflammatory disease affecting the bronchial mucosa. In asthma patients, the highest number of inflammatory cells, including eosinophils, are found in the small bronchi. According to the most recent 2006 report of the Global Initiative for Asthma, inhaled corticosteroids (ICS) remain the first-line treatment of chronic asthma. They are characterized by high lung deposition and good distribution in the small bronchi, which makes them particularly efficient in reducing chronic inflammatory infiltrate in the small airways. Good pulmonary distribution of ICS in patients with mild asthma is reflected by a better control of the disease, improvement in the quality of life, improvement in the results of pulmonary function tests, decreased levels of exhaled proinflammatory nitric oxide, lower number of inflammatory cells (including eosinophils) in the induced sputum, decrease in bronchial hyperreactivity, and decrease in exhaled air trapping observed in the computed tomographic scanning of the lungs.

Conjunctival Inflammatory Cells and Their Predictive Role For Deep Sclerectomy in Primary Open-angle Glaucoma and Exfoliation Glaucoma

To investigate the conjunctival inflammatory alterations of patients with primary open-angle glaucoma (POAG) and exfoliation glaucoma (ExG) and correlate the findings with the success of deep sclerectomy (DS) surgery and with the patients' medical history. Altogether 25 POAG and ExG patients of the prospective DS study were divided, based on the diagnosis and success of the operation, into 4 groups, POAG S (success), POAG F (failure), ExG S, and ExG F. Controls were obtained from other ophthalmologic surgery patients who did not have glaucoma, and their conjunctiva was examined to be normal. Inflammatory cell subtypes in the conjunctiva were identified and quantified by using immunohistochemistry and monoclonal antibodies: CD3 (T-lymphocyte marker), CD4 (T-helper lymphocyte marker), CD8 (T-cytotoxic lymphocyte marker), CD20 (pan-B cell marker), CD38 (plasma cell marker), CD45RA (naïve T-cell marker), and CD68 (macrophage marker). Higher numbers of inflammatory cells were found in the conjunctiva of the glaucoma patients on medical treatment compared with the normal conjunctiva of the controls. Moreover, T-lymphocytes, T-helper lymphocytes, T-cytotoxic lymphocytes, B cells, plasma cells, and macrophages were found in significantly higher numbers in patients in whom DS failed during the follow-up period of 2.5 years than those with surgical success. High numbers of cytotoxic and helper T-lymphocytes, plasma cells, and macrophages indicate a chronic inflammatory reaction in the conjunctiva of glaucoma patients. The chronic inflammation is most probably owing to the chronic topical treatment of the patients and seems to be a significant risk factor for DS surgery failure.

Multidrug resistance-associated protein-1 (MRP1) genetic variants, MRP1 protein levels and severity of COPD

BackgroundMultidrug resistance-associated protein-1 (MRP1) protects against oxidative stress and toxic compounds generated by cigarette smoking, which is the main risk factor for chronic obstructive pulmonary disease (COPD). We have previously shown that single nucleotide polymorphisms (SNPs) in MRP1 significantly associate with level of FEV1 in two independent population based cohorts. The aim of our study was to assess the associations of MRP1 SNPs with FEV1 level, MRP1 protein levels and inflammatory markers in bronchial biopsies and sputum of COPD patients.MethodsFive SNPs (rs212093, rs4148382, rs504348, rs4781699, rs35621) in MRP1 were genotyped in 110 COPD patients. The effects of MRP1 SNPs were analyzed using linear regression models.ResultsOne SNP, rs212093 was significantly associated with a higher FEV1 level and less airway wall inflammation. Another SNP, rs4148382 was significantly associated with a lower FEV1 level, higher number of inflammatory cells in induced sputum and with a higher MRP1 protein level in bronchial biopsies.ConclusionsThis is the first study linking MRP1 SNPs with lung function and inflammatory markers in COPD patients, suggesting a role of MRP1 SNPs in the severity of COPD in addition to their association with MRP1 protein level in bronchial biopsies.

Evaluation of Inflammatory Response of EDTA, EDTA-T, and Citric Acid in Animal Model

Introduction The biocompatibility of chelating agents and organic acids have been explained by a variety of methods, and suggestions for use have been based more on clinical observations and physicochemical properties than on biological aspects. The present study aimed to evaluate the inflammatory response of 17% EDTA, 17% EDTA-T, and 10% citric acid in bony defect created in rat jaws. Methods Mandibular through and through critical size defects were created bilaterally in 60 rats. Fibrinol (Baldacchi SA, São Paulo, Brazil), a cube-shaped compound of absorbable bovine fibrin foam and sodium chloride, was used as a carrier of the substances. One side had received Fibrinol (control), whereas the opposite side had received Fibrinol soaked with each substance on the 1st, on the 7th, on the 14 th, and on the 28th day ( n = 5 for each day). Hemijaws were prepared for light microscopy, and samples were stained with hematoxylin and eosin. Digitized images were analyzed with a morphometric software (ImageJ; National Institute of Mental Health, Bethesda, MD). to obtain the number of inflammatory cells per area. Comparisons were performed by using the Kruskal-Wallis test ( p = 0.05). Results For all days, 10% citric acid and 17% EDTA-T showed, respectively, the lowest and highest number of inflammatory cells per area. All tested substances and controls showed the highest inflammatory cell response on the 14th day. Conclusion Among the tested substances, 10% citric acid proved to be the less aggressive tested solution at 14 days. At 28 days, all solutions were similar, but EDTA-T kept showing the higher number of inflammatory cells.

Gentamicin-attenuated Leishmania infantum: A clinicopathological study in dogs

The clinicopathological changes following infection with an attenuated line of Leishmania infantum ( L. infantum H-line) were evaluated in mixed breed dogs. Two groups of dogs were infected intravenously (i.v.) or intradermally (i.d.) with L. infantum H-line and two control groups were infected i.v. or i.d. with L. infantum wild-type ( L. infantum WT). None of the dogs, which were infected i.v. or i.d. with L. infantum H-line, showed any abnormalities during the observation period. In contrast, two out of three dogs, which were infected i.v. with L. infantum WT, developed clinical signs of disease. In addition, no histopathological changes were seen in the liver and spleen of the dogs infected with the attenuated line of parasite, whereas the histopathological changes in the two dogs infected i.v. with L. infantum WT were severe in form and manifested by infiltration of high numbers of inflammatory cells. No promastigotes were found in cultures set up from spleens and livers of dogs infected with L. infantum H-line at 12 months post-infection, whereas promastigotes were seen in the spleen and liver cultures from 2 dogs infected i.v. with L. infantum WT. Serum levels of total IgG anti- Leishmania antibody were raised in all dogs. The antibody level in the serum of dogs infected i.v. with L. infantum WT was higher than that in dogs infected with L. infantum H-line. These results show no clinicopathological abnormalities in the dogs infected with gentamicin-attenuated L. infantum H-line. Moreover, L. infantum H-line induced IgG anti- Leishmania antibody in the dogs.

Alterations of the ocular surface epithelial MUC16 and goblet cell MUC5AC in patients with atopic keratoconjunctivitis

An increased understanding of the ocular surface at cellular level in the conjunctiva and the cornea may help explain the pathogenesis and the subsequent clinical appearance of atopic ocular allergies, which may be potentially blinding. To investigate the MUC16 and MUC5AC alterations, tear function and the ocular surface disorder in patients with atopic keratoconjunctivitis (AKC). Thirty-six eyes of 18 AKC patients as well as 28 eyes of 14 age- and sex-matched normal subjects were studied. The subjects underwent corneal sensitivity measurements, Schirmer test, tear film break-up time (BUT), fluorescein and Rose-Bengal staining of the ocular surface, conjunctival impression cytology and brush cytology. Impression cytology samples underwent periodic acid schiff and immunohistochemical staining with MUC16 and MUC5AC antibodies. Brush cytology specimens underwent evaluation for inflammatory cell numbers and quantitative real-time polymerase chain reaction (PCR) for MUC16 and MUC5AC mRNA expression. The mean corneal sensitivity and BUT values were significantly lower in patients with AKC, compared with controls (P < 0.001). Brush cytology specimens from AKC patients revealed significantly higher numbers of inflammatory cells (P < 0.001). Specimens from patient eyes showed positive staining for MUC5AC and MUC16. MUC16 mRNA expression was significantly upregulated with significant downregulation of MUC5AC mRNA expression in eyes with AKC compared with the eyes of control subjects. Ocular surface inflammation, decline in corneal sensitivity, tear film instability, changes in conjunctival epithelial MUC5AC and MUC16 mRNA expressions were thought to be important in the pathogenesis of atopic ocular surface disease.

Alterations of the ocular surface epithelial mucins 1, 2, 4 and the tear functions in patients with atopic keratoconjunctivitis

An increased understanding of the ocular surface alterations at the cellular level in the conjunctiva and the cornea, may help explain the pathogenesis and the subsequent clinical appearance of atopic ocular allergies, which may be potentially blinding. To investigate MUC 1, 2 and 4 alterations, tear function and the ocular surface disorder in patients with atopic keratoconjunctivitis. Twenty-eight eyes of 14 atopic keratoconjunctivitis patients as well as 22 eyes of 11 age-and sex-matched normal subjects were studied. The subjects underwent corneal sensitivity measurements, Schirmer's test, tear film break-up time (BUT), fluorescein and Rose Bengal staining of the ocular surface, conjunctival impression cytology and brush cytology. Impression cytology samples underwent periodic acid-Schiff and immunohistochemical staining with MUC 1, 2 and 4 antibodies. Brush cytology specimens underwent evaluation for inflammatory cell numbers and quantitative real-time-PCR for MUC 1, 2 and 4 mRNA expression. Patient eyes with fluorescein and Rose Bengal scores greater than four points were regarded to have significant epithelial disease in this study. The mean corneal sensitivity and BUT values were significantly lower in atopic patients with significant epithelial disease, compared with patients with insignificant epithelial disease and controls (P < 0.01). Brush cytology specimens from patients with significant epithelial disease revealed significantly higher numbers of inflammatory cells (P < 0.01). Specimens from patient eyes showed positive staining for MUC 1, 2 and 4. MUC 1, 2 and 4 mRNA expressions were significantly higher in eyes with significant epithelial disease compared with eyes with insignificant epithelial disease and eyes of control subjects. Ocular surface inflammation, decline in corneal sensitivity, tear film instability, changes in conjunctival epithelial MUC 1, 2 and 4 mRNA expressions were thought to be important in the pathogenesis of atopic ocular surface disease.

Susceptibility to ozone-induced airway inflammation is associated with decreased levels of surfactant protein D

BackgroundOzone (O3), a common air pollutant, induces exacerbation of asthma and chronic obstructive pulmonary disease. Pulmonary surfactant protein (SP)-D modulates immune and inflammatory responses in the lung. We have shown previously that SP-D plays a protective role in a mouse model of allergic airway inflammation. Here we studied the role and regulation of SP-D in O3-induced inflammatory changes in the lung.MethodsTo evaluate the effects of O3 exposure in mouse strains with genetically different expression levels of SP-D we exposed Balb/c, C57BL/6 and SP-D knockout mice to O3 or air. BAL cellular and cytokine content and SP-D levels were evaluated and compared between the different strains. The kinetics of SP-D production and inflammatory parameters were studied at 0, 2, 6, 12, 24, 48, and 72 hrs after O3 exposure. The effect of IL-6, an O3-inducible cytokine, on the expression of SP-D was investigated in vitro using a primary alveolar type II cell culture.ResultsOzone-exposed Balb/c mice demonstrated significantly enhanced acute inflammatory changes including recruitment of inflammatory cells and release of KC and IL-12p70 when compared with age- and sex-matched C57BL/6 mice. On the other hand, C57BL/6 mice had significantly higher levels of SP-D and released more IL-10 and IL-6. Increase in SP-D production coincided with the resolution of inflammatory changes. Mice deficient in SP-D had significantly higher numbers of inflammatory cells when compared to controls supporting the notion that SP-D has an anti-inflammatory function in our model of O3 exposure. IL-6, which was highly up-regulated in O3 exposed mice, was capable of inducing the expression of SP-D in vitro in a dose dependent manner.ConclusionOur data suggest that IL-6 contributes to the up-regulation of SP-D after acute O3 exposure and elevation of SP-D in the lung is associated with the resolution of inflammation. Absence or low levels of SP-D predispose to enhanced inflammatory changes following acute oxidative stress.

The influence of functional groups of self‐assembled monolayers on fibrous capsule formation and cell recruitment

The contribution of the surface chemistry of an implant to the thickness of the fibrous capsule formed after implantation was herein investigated. For that, self-assembled monolayers (SAMs) of alkanethiols on gold with different terminal functional groups (COOH, OH, and CH(3)) were used. These surfaces were implanted in subcutaneous air pouches of BALB/c mice and the ensuing fibrous capsules were evaluated and compared with the initial inflammatory response caused by the implant. The thickness of the fibrous capsules that are under organization around the implant was measured 1 week after implantation by histology. Inflammatory exudates were collected from the air pouches 24 h after the implantation of SAMs and were analyzed by flow cytometry. A significant increase in the thickness of fibrous capsules was seen around implanted CH(3)-terminated SAMs, and also in gold surfaces, in comparison with the air pouch wall of sham-operated mice and of COOH- and OH-covered SAMs. The CH(3)-coated implants also recruited higher numbers of inflammatory cells; this enhancement involved a significant number of Mac-1(+) cells. Our data indicate that implant surfaces coated with CH(3) induce thick fibrous capsules and this may be the result of the stronger inflammatory effect of CH(3) in comparison with COOH or OH chemical groups.

Inflammatory cell recruitment and adhesion to methyl‐terminated self‐assembled monolayers: Effect of implantation time

The contribution of methyl groups in implant-triggered inflammation was investigated in vivo using self-assembled monolayers (SAMs) of alkanethiols on gold. The CH(3)-coated implants were inserted in an air-pouch cavity induced in BALB/c mice. The in situ inflammatory response was monitored 24, 48, and 72 hours later. Inflammatory cells recovered from the air pouches were counted and observed by light microscopy. The cellularity of the implant surfaces was defined by scanning electron microscopy (SEM). In comparison with gold implants, the CH(3)-coated SAMs recruited a significantly higher number of inflammatory cells. Polymorphonuclear leukocytes (PMN) were more numerous than mononuclear cells (Mo) in the exudates recovered from the air pouches with CH(3)-coated SAMs. The opposite PMN/Mo proportion was observed in air pouches of the two control groups (mice receiving gold implants or sham-operated animals). A low density of adherent cells was seen on CH(3)-coated implants, with no significant quantitative differences during the time course of the study. In contrast, the gold-coated surfaces were covered with numerous cells during all of the 3 days of the inflammation. In conclusion, implants with CH(3) surfaces are likely to induce PMN-dominated local acute inflammation but these surfaces are not associated with a significant adherence of leukocytes to the implant.

A Role for Angiogenesis in Hemophilic Synovitis.

Hemarthrosis, or bleeding into a joint, is the most common manifestation of hemophilia. Recurrent hemarthroses and synovial proliferation leads to the formation of a thickened synovial pannus, or synovitis, followed by destructive infiltration into the adjacent cartilage and bone, a condition known as hemophilic arthropathy. While the clinical sequence of events in hemophilic joint disease is understood, the pathogenesis of synovitis has not yet been elucidated. As such, there is scant objective evidence for the selective application of strategies like prophylaxis or isotopic synovectomy (IS) to prevent imminent joint deterioration. In other fibroproliferative disorders such as rheumatoid arthritis, osteoarthritis, psoriatic arthritis, and tumor growth, angiogenesis and the concomitant recruitment of bone marrow-derived (BMD) progenitors has been implicated in disease progression. Here, for the first time, we report direct evidence for the involvement of angiogenesis in the development and sustenance of hemophilic synovitis. Histological sections of synovial tissue from patients with hemophilic synovitis and arthropathy were highly vascularized and contained a high number of inflammatory cells, predominantly CD68+ macrophages, which co-localized with secreted pro-angiogenic factors including vascular endothelial growth factor (VEGF), basic fibroblastic growth factor (bFGF), matrix metalloproteinase-9 (MMP-9), tumor necrosis factor-alpha (TNF-a) and cyclooxygenase-2 (COX-2). Hemophiliacs with joint disease exhibited a five-fold increase in 12 circulating angiogenesis-related cytokines compared to individuals with a bleeding disorder without joint disease and to healthy controls, as profiled by a protein array. Likewise, plasma VEGF and MMP-9, critical mediators of BMD progenitor mobilization and important pro-angiogenic factors, were significantly elevated in hemophiliacs with joint disease compared to the non-joint disease groups (Table 1). Accordingly, hemophiliacs with joint disease (n=9) exhibited an increased percentage of circulating CD34+ progenitor cells as compared to control groups (n=6). Finally, in a functional in vitro assay, plasma from hemophiliacs with joint disease showed a markedly enhanced capacity to elicit an angiogenic response from human umbilical vein endothelial cells (HUVECs) as evidenced by the induction of morphogenetic changes resembling capillary-like structure tube formation and cord-like processes connecting cellular nodes. These data collectively suggest that angiogenesis may play an important role in the development of synovial proliferation and synovitis in hemophilia. Indexing circulating angiogenic growth factors and CD34+ precursors may provide effective means of detecting early synovial proliferation and identifying candidates for early intervention with prophylaxis or IS. Ultimately, anti-angiogenic agents may provide a novel preventative treatment strategy for hemophilic arthropathy.Table 1. Plasma concentrations of pro-angiogenic factors.FactorHemophiliacs w/ joint diseaseBleeding disorders w/o joint diseaseHealthy controlsP1P2VEGF, pg/ml93.2±16 (n=60)24.7±3 (n=42)24.7±3 (n=42)0.0010.026MMP-9, ng/ml157.8±53 (n=27)36.0±6 (n=27)34.8±8 (n=20)0.0290.050P1 indicates joint diseased hemophiliacs versus bleeding disorders w/o joint disease; P2 versus healthy controls.

Inflammatory responses and cell adhesion to self-assembled monolayers of alkanethiolates on gold

The acute inflammatory response and the adhesion of cells to self-assembled monolayers (SAMs) of well-defined surface chemistry was studied in vivo using a rodent air-pouch model of inflammation. SAMs with three different terminal functional groups (OH, COOH and CH 3) were implanted in subcutaneous air pouches induced in BALB/c mice. After 24 h, inflammatory cells were recovered from the air pouches and the implants were removed and prepared for observation by scanning electron microscopy (SEM). The implants coated with OH and CH 3, were found to cause the highest recruitment of inflammatory cells into the subcutaneous pouches. Polymorphonuclear neutrophils (PMNs) leukocytes predominated over mononuclear cells in inflammatory exudates of SAMs-coated implants, the opposite being found in uncoated implants (controls). CH 3-coated implants induced the highest number of inflammatory cells and also the largest percentage of PMNs seen in the subcutaneous pouches. Control and OH-covered implants presented the higher densities of attached inflammatory cells detected by SEM. In contrast, the CH 3-coated implants showed a very low density of cells adherent to the implant surface. We conclude that the chemical nature and the degree of hydrophobicity of the surface of implants modulate both the local acute inflammatory reaction and the adhesion of leukocytes.

Immunohistochemistry, ultrastructure and pathology of gills of Abramis brama from Lake Mondsee, Austria, infected with Ergasilus sieboldi (Copepoda).

Immunohistochemical, ultrastructural and pathological studies were carried out on the gills of bream Abramis brama (L.) from Lake Mondsee, Austria, that were naturally infected with Ergasilus sieboldi Nordmann, 1832. Of a total of 14 specimens of bream examined, the gills of 7 (50%) were parasitized with this copepod and the intensity of infection ranged from 1 to 23 crustaceans per host. Histopathological investigations of infected gill showed extensive tissue damage due to attachment and feeding of the crustacean. Parasites attached close to the base of filaments near the gill arch. Pressure exerted by the ectoparasite attached to the lateral margin of the gill filaments induced atrophy of the secondary lamellae. Tissue reactions included hyperplasia and mucous cell proliferation of the respiratory epithelium. Mucous cells displayed an intense immunohistochemical reactivity with the anti-nitric oxide synthase antibody. In parasitized primary and secondary lamellae, a high number of eosinophilic granular cells and rodlet cells were noticed. Rodlet cells represent an inflammatory cell type closely linked to other piscine inflammatory cells. Presence of a high number of inflammatory cells at the site of E. sieboldi attachment is related to intense host cellular reaction.

Experimental Autoimmune Labyrinthitis: Assessment of Molecular Size of Autoantigens in Fractions of Inner Ear Proteins Eluted on the Mini Whole Gel Eluter

In order to determine the molecular size of the causative autoantigens of experimental autoimmune labyrinthitis, crude inner ear antigen was separated into 14 fractions and the constituent molecules were identified by means of sodium dodecyl sulfate-polyacrylamide gel electrophoresis using the Mini Whole Gel Eluter. The mean total protein recovery was approximately 66%. Sensitization with 55-65 kDa proteins induced the highest number of infiltrating cells among the fractions and sensitization with 38-45 kDa proteins induced the second highest number of inflammatory cells. These results suggest that 38-45 kDa and 55-65 kDa proteins are the causative autoantigens of experimental autoimmune labyrinthitis.

Experimental Autoimmune Labyrinthitis: Assessment of Molecular Size of Autoantigens in Fractions of Inner Ear Proteins Eluted on the Mini Whole Gel Eluter

In order to determine the molecular size of the causative autoantigens of experimental autoimmune labyrinthitis, crude inner ear antigen was separated into 14 fractions and the constituent molecules were identified by means of sodium dodecyl sulfate-polyacrylamide gel electrophoresis using the Mini Whole Gel Eluter. The mean total protein recovery was , 66%. Sensitization with 55-65 kDa proteins induced the highest number of infiltrating cells among the fractions and sensitization with 38-45 kDa proteins induced the second highest number of inflammatory cells. These results suggest that 38-45 kDa and 55-65 kDa proteins are the causative autoantigens of experimental autoimmune labyrinthitis.

Inducible nitric oxide synthase is expressed in joints of goats in the late stage of infection with caprine arthritis encephalitis virus.

We have studied the expression of the inducible form of nitric oxide synthase (iNOS) in joints of goats infected with the caprine arthritis encephalitis virus (CAEV). Nitric oxide generated by iNOS is thought to play an important role in the pathogenesis of various types of arthritis, especially rheumatoid arthritis (RA) in humans. Surprisingly, iNOS immunoreactivity was found only in joints of long-term infected goats with severe clinical arthritis, whereas-despite the presence of high numbers of inflammatory cells in the synovial tissue-no iNOS immunoreactivity was detected in mildly arthritic and in short-term experimentally infected goats. Most iNOS-positive cells expressed neither MHC class II nor CD68, which suggests that they were fibroblast-like synoviocytes. In situ hybridization studies showed that there was no correlation between iNOS immunoreactivity and detectable virus expression in the joint. In addition, infection of macrophages in vitro-the major host cells of CAEV in vivo-did not lead to increased iNOS mRNA expression. In response to stimulation, similar levels of iNOS expression were observed in infected and in uninfected macrophages. These findings suggest that the expression of iNOS is a feature of late-stage chronic arthritis and is not involved in the development of the inflammatory lesions. Both the lack of co-localization of iNOS protein and viral transcripts in the joint and the finding that CAEV does not stimulate the expression of iNOS in vitro further suggest that iNOS is not directly induced by the virus or the anti-viral immune response in the joint, that it may well, however, be involved in tissue remodelling or scar formation.

Immunohistological and morphometric analysis of inflammatory cells in rapidly progressive periodontitis and adult periodontitis.

The purpose of this study was to localize, characterize, and quantify in situ the inflammatory cells in the gingival connective tissue prior and subsequent to the initial therapy of ten patients with rapidly progressive periodontitis (RPP) and five patients with adult periodontitis (AP). Using immunohistological techniques, the amount of T lymphocytes, alphabeta-T lymphocytes, gammadelta-T lymphocytes, B lymphocytes, and plasma cells was determined at the beginning of the periodontal therapy (baseline) and at the time of periodontal surgery. Furthermore, the distribution of collagen types I, III, V, and VI was investigated using transmission electron microscopy. At baseline, patients with RPP revealed much higher numbers of inflammatory cells than patients with AP. During initial therapy of patients with RPP, the amount of T cells, alphabeta-T cells, and gammadelta-T cells was reduced significantly (P<0.05). Biopsies of patients with AP revealed a statistically significant reduction of all cell types, except alphabeta-T cells and gammadelta-T cells in the deep connective tissue. The transmission electron microscopy of biopsies from patients with RPP and AP with severe inflammation taken at baseline revealed that collagen types I and III were destroyed nearly completely in areas with leukocyte infiltration, whereas collagen types V and VI revealed a more pronounced labeling reaction. The results revealed that, during initial therapy, the amount of inflammatory cells was reduced significantly more in biopsies of patients with AP than in patients with RPP. At baseline, the inflamed gingival tissue consists mainly of collagen types V and VI in areas with infiltrates of inflammatory cells.

INFECTION, NEUTROPHILS, AND HEMATOPOIETIC GROWTH FACTORS IN THE PATHOGENESIS OF NEONATAL CHRONIC LUNG DISEASE

Continued definition of the biochemical and molecular mechanisms underlying the development of chronic lung disease (CLD) has persuaded investigators that inflammatory cells and mediators are key factors in the pathophysiology of the disease. High numbers of inflammatory cells and their products are present in the airways of ventilated neonates with respiratory distress syndrome and precede the development of CLD. This article reviews the mechanisms underlying neutrophil recruitment in the lungs of ventilated preterm infants with respiratory distress syndrome and the injurious effects that these cells can produce on lung parenchyma with special emphasis on the development of CLD. The role of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor is stressed as a pivotal mechanism of neutrophil recruitment and activation.

TUMOUR NECROSIS FACTOR-α EXPRESSION IN IDIOPATHIC DILATED CARDIOMYOPATHY: CORRELATION TO MYOCARDIAL INFLAMMATORY ACTIVITY

High numbers of inflammatory cells are found in a subgroup of patients with idiopathic dilated cardiomyopathy (IDCM). We hypothesized that the extent of inflammation is linked to myocardial TNF-α expression in human IDCM. Fourteen patients who consecutively underwent endomyocardial biopsy (EMB) were stratified into two groups—a group with low and a group with high myocardial inflammatory index (MII)—based on immunohistochemical analysis of cellular infiltration and HLA I and II expression. Myocardial TNF-α messenger RNA (mRNA) expression was determined by reverse transcriptase polymerase chain reaction, TNF-α protein was localized by immunohistochemistry and TNF-α serum levels were measured by EIA. IDCM patients with a high MII (n=6) showed a 1.9-fold higher TNF-α mRNA expression when compared to IDCM patients with low MII (n=8, P=0.020). TNF-α protein was detected at perinuclear regions of cardiac myocytes and the endothelium. TNF-α serum levels were 3.0 (0.55) pg/ml in patients with high MII compared to 1.35 (0.20) pg/ml in patients with low MII (P=0.017). According to immunolocalization cardiac myocytes and the endothelium seem to be the major source of TNF-α production. Whether the elevated systemic level of TNF-α found in patients with high MII are elaborated by the myocardium or are produced by other tissues representing a general immune activation is not clear.