Search PubMed⌕ Search

Biomedical subjects

C Kroegel

Publications and source records attributed to C Kroegel.

At least 73 records · Page 4Linked to original sources
PubMed1995

[Immunopathogenesis of allergic bronchial asthma. Detection of activated CD25-CD4 lymphocytes and release of cytokines in the bronchoalveolar space following segmental allergen challenge].

The aim of this study was to investigate the fundamental processes underlying the inflammatory response to allergen in mild non-symptomatic asthmatics, using a new model entailing endobronchial segmental provocation. Ten asymptomatic asthmatic volunteers (8 male, 2 female; mean age 28.2 [24-41] years) were challenged employing the segmental allergen provocation technique. 250 PNU in 5 ml 0.9% NaCl solution of either birch (n = 8) or grass (n = 2) pollen were instilled into one segment. As control, only the solvent was instilled into a segment of the contralateral lung. Bronchoalveolar lavage (BAL) with 100 ml prewarmed saline was performed 10 min and 18 h after allergen provocation. The cellular distribution and activation state in BAL fluid and peripheral blood was analysed by immunofluorescence and flow cytometry. The concentration of various cytokines was determined in the BAL fluid using ELISA and bioassays. In blood, segmental allergen provocation led to an increase both in numbers of neutrophils (3833 cells/microliters vs 6830 cells/microliters; P < 0.005) and activated IL-2R expressing (CD25+) CD4+ T cells (3.6% vs 4.8% of all CD4+ lymphocytes; P < 0.05). No change was observed in eosinophils and other leukocytes and lymphocyte subsets. In contrast, a significant 30-fold increase in eosinophils (0.39 x 10(6) vs 11.5 x 10(6) cells/100 ml; P < 0.01) and a twofold increase in CD25+ CD4+ T cells (P < 0.05) were found in BAL samples 18 h after segmental allergen challenge, when compared to the control segment. Analysis of the cytokine profile revealed significantly increased levels of several cytokines. Allergen challenge of extrinsic asthmatic subjects causes differentiation of activated CD25+ CD4+ lymphocytes which may contribute to the pathogenesis of the asthmatic inflammation through the release of various cytokines.

Adult↗
PubMed1995

Immunocytochemical characterization of malignant mesothelioma and carcinoma metastatic to the pleura: IOB3--a new tumor marker.

We have tried to find a reliable panel of markers that would allow distinction between mesotheliomas and carcinomas metastatic to the pleura. In a prospective study, we evaluated 54 pleural effusions: In 27 of the patients, a diagnosis of histologically proven metastatic carcinoma was subsequently established, 7 patients had biopsy-proven malignant mesotheliomas and 20 had benign, reactive effusions whose benign etiologies were established by more than 2 years clinical follow-up. The MAb (monoclonal antibody) IOB3 proved to be diagnostic for carcinomas in all 27 cases (100%), whereas CEA (carcinoembryonic antigen) expression was found in only 22 out of 27 (81%). None of the malignant mesotheliomas, nor benign reactive mesothelial cells reacted with these two markers. All carcinomas, as well as one malignant mesothelioma, reacted with the MAb HEA125. Antibodies against 12 single cytokeratins, vimentin, and EMA (epithelial membrane antigen) were not helpful in the differentiation between malignant mesotheliomas and malignant carcinomatous pleural effusions. We conclude that adding the antibody IOB3 to the CEA assay should allow a reliable differentiation between these two entities.

Adult↗
PubMed1995

Mechanisms of human eosinophil activation by complement protein C5a and platelet-activating factor: similar functional responses are accompanied by different morphologic alterations.

The complement system is an important amplification system for the propagation of allergic as well as pseudoallergic inflammatory reactions. In the present study, the effect of the major anaphylatoxin C5a was compared with that of platelet-activating factor (PAF) on highly purified eosinophils (> or = 95%) by functional as well as morphologic criteria. Upon stimulation with C5a, eosinophils maintained their spheric structure, developing short, pseudopodia-like protrusions, whereas PAF induced the generation of a number of digitating protrusions. As shown by functional and ultrastructural assay systems, both stimuli provoked significant extracellular and intracellular H2O2 production in eosinophils, which was inhibited by cytochalasin B. With C5a, a pronounced H2O2 production was detected within the small cytoplasmic vesicles, whereas PAF-induced H2O2 production was observed on the outer surface of the plasma membrane in the contact zones between adjacent cells. Morphologic signs of degranulation induced by C5a and PAF were accompanied by the significantly increased release of eosinophil cationic protein and eosinophil peroxidase in the presence of cytochalasin B. Like PAF, C5a induced a significant production of reactive oxygen species in eosinophils, as measured by lucigenin-dependent chemiluminescence (CL) responses in eosinophils. Maximal responses, comparable with those of interleukin-5 (100 U/ml), were observed at concentrations of 10(-5)-10(-6) and 10(-7)-10(-8) M for PAF and C5a, respectively. Separation of eosinophils by discontinuous density gradients revealed the existence of two hypodense eosinophil populations, one of them showing significantly reduced CL responses upon stimulation with C5a and PAF. In addition, CL responses upon stimulation with C5a and PAF were abrogated by cytochalasin B, staurosporine, and wortmannin, and were almost completely blocked by pertussis toxin. In conclusion, these data indicate that C5a induces events in human eosinophils comparable to those induced by PAF in the assay systems tested. Thus, C5a, generated after activation of the complement system, may be of major importance for the eosinophil activation observed in eosinophil-related disease.

Blood Proteins↗
PubMed1995

T cells and cytokines in bronchoalveolar lavage fluid after segmental allergen provocation in atopic asthma.

Increasing evidence suggests a role for activated T cells and cytokines in the regulation of eosinophilic inflammation in asthma. In this study, we investigated the distribution of leukocytes, lymphocytes, their activation state, and the cytokine profile in BAL from 10 atopic asthmatics with positive skin prick tests and elevated specific IgE levels to birch or grass pollen. Using segmental allergen challenge, 250 PNU of the appropriate allergen or saline were instilled into different segments, which were lavaged 10 min (10 min) and 18 h (18 h) after allergen challenge or 18 h after saline challenge (C). In peripheral blood the number of neutrophils and activated IL-2R+/CD4+ T cells increased significantly 18 h after allergen provocation; there was no change in eosinophils, other leukocytes, or lymphocyte subsets. In contrast, numbers of eosinophils, neutrophils, and IL-2R+/CD4+ T cells increased significantly in BAL samples at 18 h. The numbers of neutrophils and eosinophils were not significantly different in the lavage performed at 10 min and at C. Analysis of cytokines in concentrated BAL fluid revealed significantly increased levels of IL-5, IL-2, IL-1, TNF-alpha, IL-6, IL-8, and GM-CSF, but not of IL-4 and IFN-gamma at 18 h compared with those at C and at 10 min. The correlation between IL-5 levels, eosinophil numbers, and activated T cells supports a role for T-cell-derived IL-5 in causing tissue eosinophilia in allergic asthma.

Adult↗
PubMed1994

Cellular and immunological markers of allergic and intrinsic bronchial asthma.

Based on a growing body of evidence, allergic as well as intrinsic bronchial asthma have recently been defined as chronic persistent inflammatory disorders. Agreement has been reached that asthma can no longer be equated with bronchospasm only, and that the absence of reversibility of airflow obstruction does not exclude bronchial asthma. Bronchial hyperreactivity, on the other hand, although common to the vast majority of asthmatics, is not specific for bronchial asthma and provocation tests to measure bronchial hyperreactivity are not suited for routine monitoring of bronchial asthma. The clinical features of asthma are related to cellular as well as to soluble parameters of bronchial inflammation. Therefore, means of assessing and monitoring asthmatic inflammation have been investigated. Since eosinophils, T lymphocytes, mast cells, macrophages, neutrophils, epithelial cells, and structural cells, as well as various proinflammatory mediators and proteins, have been implicated in the pathogenesis of bronchial asthma, it has been anticipated that several of these cells or mediators might be either diagnostic of bronchial asthma or could serve as markers to monitor the underlying bronchial inflammation. Currently there is no diagnostic marker of bronchial asthma, which, on its own, either confirms or excludes bronchial asthma with appropriate sensitivity and specificity. Clinically the most reliable feature of bronchial asthma that seems to be related closely to the symptomatology still is the presence of eosinophils in peripheral blood, and especially in sputum. Eosinophil-derived products, particularly eosinophil granule proteins, have been investigated as markers of eosinophil participation in the pathogenesis of asthma and, comparable to eosinophil numbers themselves, are possible predictors of impending exacerbations of allergic, as well as intrinsic bronchial asthma. However, clinically their precise value in diagnosing and monitoring of bronchial asthma has not been documented convincingly and requires further investigation. Increasing data suggest that the regulation of eosinophilia is largely conveyed by interleukin-5 (IL-5) released from activated T-helper lymphocytes and possibly other cells. Therefore, T-lymphocyte activation, and especially assessment of systemic and local IL-5 levels, might be of diagnostic value and possibly useful in monitoring of inflammation in bronchial asthma in the future. A possible role and future applications for other markers of inflammation not related to eosinophils in monitoring or diagnosing bronchial asthma need to be established.

Adult↗
PubMed1994

Blood and bronchoalveolar eosinophils in allergic subjects after segmental antigen challenge: surface phenotype, density heterogeneity, and prostanoid production.

Eosinophil infiltration into the airways has been implicated in the pathophysiology of asthma. To improve our understanding of the function of eosinophils in asthma, we have compared the phenotype and function of eosinophils obtained simultaneously from blood and bronchoalveolar lavage (BAL) of allergic subjects 19 hours after segmental lung allergen challenge. Eosinophils were purified by discontinuous density gradient centrifugation, and their distribution at various layers was quantitated. Eosinophils at the 1.080 to 1.085 gm/ml interfaces from blood and BAL (purity > 70%) were analyzed by immunofluorescence and flow cytometry for several surface markers including adhesion-activation antigens. Eosinophils in BAL from antigen-challenged sites were markedly increased compared with control diluent-challenged BAL sites (0.3% +/- 1% vs 28.1% +/- 9.7%, n = 12, p < 0.002), and a greater percentage were hypodense (specific gravity < 1.080 gm/ml) than in peripheral blood (51.3 +/- 5.3 vs 19.0 +/- 4.4, n = 15, p < 0.01). In vitro, resting and activated BAL eosinophils biosynthesized less thromboxane B2 than blood eosinophils. Although both BAL and blood eosinophils expressed similar levels of Fc gamma RII (CD32), CD11a, and CD45, resting levels of Mo-1 (CD11b) were upregulated on BAL eosinophils (mean fluorescence intensity, 316% +/- 48% of blood eosinophils, n = 5, p < 0.05). Blood eosinophils stimulated in vitro with 1 mumol/L platelet activating factor or N-formyl-methionyl-leucyl-phenylalanine achieved levels of CD11b expression similar to those of BAL eosinophils. In contrast, CD11b expression on BAL eosinophils could not be further increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Bronchoalveolar lavage cytology and immunocytology in pulmonary tuberculosis.

Limited data on the cellular and immunocytologic characteristics of bronchoalveolar lavage (BAL) fluid in pulmonary tuberculosis have been reported. We therefore studied 40 patients with active disease. BAL fluid differential cell counts and lymphocyte subsets were determined. The findings were compared with data from 47 patients with active sarcoidosis and 30 healthy control subjects. The proportion of lymphocytes was increased in both diseases (p < 0.001 versus control subjects) but with no difference compared to one another. The CD4/CD8 ratio was normal in 33 of 40 patients with pulmonary tuberculosis in contrast to sarcoidosis, with an increased ratio in 33 of 47 patients. HLA-DR+ T lymphocytes were significantly increased in both pulmonary tuberculosis and sarcoidosis (p < 0.05 versus control group). The proportion of CD57+ lymphocytes was normal in all study groups. We conclude that pulmonary tuberculosis and sarcoidosis are characterized by an increased percentage of lymphocytes in BAL fluid with a similar proportion of activated T cells. In contrast to active sarcoidosis, in which an elevated CD4/CD8 ratio is characteristic, in the majority of pulmonary tuberculosis patients the CD4/CD8 ratio is within the normal range.

Adult↗
PubMed1994

Modulatory role of protein kinase C on the signal transduction pathway utilized by platelet-activating factor in eosinophil activation.

To determine the role of protein kinase C (PKC) in the signal transduction in eosinophil pathways, we have assessed the effects of the phorbol ester phorbol 12-acetate 13-myristate (PMA) on guinea pig peritoneal eosinophils challenged with platelet-activating factor (PAF). Pretreatment with PMA completely inhibited the PAF-induced release of eosinophil peroxidase (EPO) and superoxide anions and the rise in intracellular Ca2+ concentration ([Ca2+]i), with IC50s of 2 to 10 nM. This inhibition was reversed when the cells were preincubated with the PKC inhibitor staurosporine for 5 min before the addition of PMA. Staurosporine also inhibited PAF-induced EPO release but not the rise in [Ca2+]i. The inactive ester 4 alpha-phorbol 12,13-didecanoate had no inhibitory effect on eosinophil activation. Finally, PMA inhibited the binding of the PAF antagonist [3H]WEB 2086 to intact eosinophils. Taken together, these data suggest that PKC may have a physiologic role in regulating PAF-induced eosinophil responses through expression of PAF receptors on the cell surface.

Alkaloids↗
PubMed1994

Pulmonary immune cells in health and disease: the eosinophil leucocyte (Part I).

Increasing evidence has accumulated to suggest that eosinophils play a key role in the pathogenesis of asthma and other pulmonary diseases by damaging infiltrated bronchial tissue and lung parenchyma. The first part of this review on eosinophils describes the cellular characteristics and properties of the cell, which help in understanding its role in disease. The article focuses on origin, maturation and differentiation of the eosinophil, its morphological and phenotypical properties, as well as its preformed and newly generated mediators of inflammation. The cause and putative significance of eosinophil heterogeneity in respect to function and density will also be discussed. In addition, the naturally occurring mediators through which eosinophils are activated and communicate with other inflammatory cells are outlined. The first part closes with new aspects of eosinophil recruitment from the circulation into perivascular tissue, including nonselective and putative selective adhesion mechanisms and chemotaxis.

Eosinophils↗
PubMed1994

Pulmonary immune cells in health and disease: the eosinophil leucocyte (Part II).

The second part of this review on eosinophils focuses on biological cell functions and surveys the various deleterious mechanisms involved in the eosinophil-dominated inflammatory reaction. It discusses the possible pathogenic role of eosinophils in several eosinophil-related diseases, such as parasitic infections, interstitial lung disorders and bronchial diseases, such as parasitic infections, interstitial lung disorders and bronchial diseases, graft rejection, vasculitic granulomatous disorders, pleural effusion, and bronchogenic tumours. The final section of the article highlights the possible recent pharmacological and future therapeutic approaches in modifying eosinophil recruitment and function.

Eosinophils↗
PubMed1994

Pulmonary immune cells in health and disease: mast cells and basophils.

Mast cells and basophils are multifunctional immune cells and have been implicated in the pathogenesis of asthma and other pulmonary diseases. Although they are derived from distinct lineages, they share a number of important features which justifies discussing them collectively. This review covers the cellular characteristics and biological properties of both cell types, including origin, maturation and differentiation, morphological and phenotypical properties, as well as their capacity to secrete preformed and newly generated mediators of inflammation. In addition, the mechanisms of cell activation and priming of mast cells and basophils will be outlined, as well as the putative mechanisms through which both cell types communicate with other inflammatory cells. The final section of the review focuses on the possible pathogenetic role of mast cells and basophils in several pulmonary diseases, such as parasitic infections, allergic diseases, pulmonary fibrosis and malignant disorders.

Animals↗