Search PubMed⌕ Search

Biomedical subjects

C Kroegel

Publications and source records attributed to C Kroegel.

At least 91 records · Page 5Linked to original sources
PubMed1994

[Cell biology and function of eosinophilic granulocytes in immunologic inflammation].

In recent years, increasing evidence has accumulated to suggest that the eosinophil represents a potent cytotoxic effector cell which plays a key role in the pathogenesis of pulmonary diseases as well as other human disorders. Beside contributing to antiparasitic host defense, eosinophils can prove detrimental to a number of host organs and tissues via release of their preformed basic proteins as well as de novo generated lipid mediators or oxygen radicals. Eosinophil effector functions are stimulated by certain lipid mediators and cytokines released by other cells in the course of active disease. In addition to their effector functions, eosinophils may have other functions in immune responses. Synthesis and expression of class II proteins of the major histocompatibility complex (MHC) may enable eosinophils to serve as antigen-presenting cells, i.e. to the antigens that appear at mucosal surfaces. In addition to collaborative interactions with lymphocytes, CD4-expressing eosinophils may elaborate cytokines that can effect cells within their tissue milieu. In conclusion, the evolving understanding of eosinophils indicates that eosinophils may not only serve as end-stage effector cells but also interact cooperatively with other cellular tissue elements in related diseases.

Asthma↗
PubMed1994

[The immunologic role of eosinophilic granulocytes within the scope of inflammatory lung diseases].

Although identified over a hundred years ago, the precise role of the eosinophil in eosinophil-associated diseases still remains undefined. However, the results of modern cellular, immunological, and biochemical investigations have suggested that eosinophils contain unique constituents and functional adaptions through which eosinophils gain a profound cytotoxic capacity. This property may not only be crucial for the host defence mechanism against helminthic infections but may also be involved in the pathogenesis of chronic inflammation associated with allergic reaction and other eosinophilic disorders. There is increasing evidence available that the eosinophil may cause damage to host tissue and elicit tissue fibrosis. The eosinophil appears to adapt certain general cellular characteristics during its ontogeny and participation in inflammatory reactions, such as hypodensity, expression and induction of surface markers and adhesion molecules. In addition, there is evidence that the eosinophil may undergo a shift between hypo- and hyperreactivity states. Factors regulating the level of eosinophil activation may include both lipid mediators and cytokines released by macrophages, mast cells, platelets, endothelial cells, and T lymphocytes. The rapidly evolving understanding of the functional properties of the eosinophil will further help to define the pathogenesis of certain eosinophilic disorders and may provide the basis for new therapeutic strategies in eosinophilic disorders.

Cytotoxicity, Immunologic↗
PubMed1993

Asthma.

Explore the source record for details and available documents.

Asthma↗
PubMed1993

Ultrastructural characterization of platelet-activating factor-stimulated human eosinophils from patients with asthma.

1. Purified human eosinophils from asthmatic patients were stimulated with platelet-activating factor in vitro and examined for morphological changes by transmission electron and light microscopy. Changes were also evaluated by morphometric analysis and were related to the platelet-activating factor-stimulated release of granular eosinophil cationic protein. 2. Stimulation of eosinophils with platelet-activating factor induced a dose-dependent shape change, including the elongation of cells, loss of microvilli and the formation of lamellipodia. This effect was maximal at 25 min and was reversible. 3. Stimulation with platelet-activating factor also induced granule movement to the cell periphery and fusion of adjacent granules. Granules became swollen and vesiculated, whereas both the matrix and core showed evidence of solubilization. 4. There was a time-dependent secretion of eosinophilic cationic protein from human eosinophils upon stimulation with platelet-activating factor which occurred without significant lactate dehydrogenase release. 5. Morphometric analysis of the transmission electron micrographs indicated a significant reduction in cytoplasmic area after 10 min of incubation with platelet-activating factor from 39.0 +/- 1.7 microns 2 for untreated eosinophils to 33.2 +/- 2.3 microns 2 (P < 0.02) for platelet-activating factor-treated cells, underscoring the observation that the cells change from spherical to ellipsoidal. No significant increase in the perimeter of the cells was found. 6. The number of granule-profiles in platelet-activating factor-stimulated eosinophils was slightly reduced when compared with control, and an increase in granule area was observed 10 min after platelet-activating factor challenge (0.215 +/- 0.011 microns 2 versus 0.246 +/- 0.016 microns 2).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Comparison of sputum-ECP levels in bronchial asthma and chronic bronchitis.

Eosinophil cationic protein (ECP) is a cationic protein secreted by eosinophils with toxic properties for the respiratory epithelium. Sputum-ECP levels have been shown to correlate inversely with airflow obstruction in asthma. In the present study we investigated whether ECP concentrations are different between asthmatic patients and patients with chronic bronchitis. Sputum-ECP concentrations from seven patients with bronchial asthma and seven patients with chronic bronchitis matched for FEV1 were compared (FEV1 Asthma: 66.1 +/- 29.0% of predicted; FEV1 Chronic Bronchitis: 65.2 +/- 33.3% of predicted; p = n.s.). Furthermore, sputum-ECP levels in 4 asthmatic patients with severe airflow obstruction and in 1 patient with chronic bronchitis were measured before and after initiation of a 7-day oral therapy with methylprednisolone 20 mg BID. Changes in sputum-ECP values were compared with changes in FEV1 in these 5 patients. Sputum-ECP levels and pulmonary function were measured as previously described (Am Rev Respir Dis 1992: 145: 604). Sputum-ECP levels from asthmatics were significantly elevated compared with patients with chronic bronchitis: asthma: 893.4 +/- 346.2 micrograms/l per g sputum; chronic bronchitis: 30.0 +/- 8.5 micrograms/l per g sputum (p = 0.002). The degree of airway obstruction correlated with the sputum-ECP levels in asthmatic (r = 0.76, p = 0.05), but not in the patients with chronic bronchitis (r = 0.24, p = n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Platelet-activating factor-induced human eosinophil activation. Generation and release of cyclo-oxygenase metabolites in human blood eosinophils from asthmatics.

The spontaneous and stimulated generation of fatty acid cyclo-oxygenase pathway-derived products of arachidonic acid from highly purified (91.6 +/- 1.3%, n = 23) human blood eosinophils obtained from asthmatics were examined using combined gas chromatography/mass spectrometry. Under resting conditions, eosinophils spontaneously generated 0.24 +/- 0.10 pg prostaglandin E2 (PGE2), 0.51 +/- 0.20 prostaglandin D2 (PGD2), 0.35 +/- 0.10 pg prostaglandin F2 alpha (PGF2 alpha) and 8.5 +/- 2.2 pg thromboxane B2 (TXB2), the stable metabolite of TXA2 per 10(6) cells. In contrast, 6-keto-prostaglandin F1 alpha and 9 alpha,11 beta-prostaglandin F2 were not detectable. Stimulation of eosinophils with platelet-activating factor (PAF) for 5 min induced a two- to sixfold increase in the biosynthesis of prostanoids. More than 95% of the generated prostanoids were released into the surrounding medium. The response to PAF was inhibited by the PAF receptor antagonist WEB 2086 (1 microM). The fatty acid cyclo-oxygenase inhibitor, ibuprofen, abolished both the spontaneous and PAF-stimulated generation of prostanoids by eosinophils. LTB4, PMA and calcimycin also produced an increase in prostanoid production, whereas lyso-PAF, the PAF precursor and metabolite, failed to induce prostanoid generation over basal production. In conclusion, the results demonstrate that PAF potently activates human eosinophils to generate and release several fatty acid cyclo-oxygenase metabolites of the arachidonic acid pathway, with TXB2 being the most abundant. These data are in agreement with previous observations suggesting that PAF may be an important stimulus for prostanoid release by the eosinophil in allergic diseases such as asthma.

Asthma↗
PubMed1992

Morphology and density features of eosinophil leukocytes in eosinophilic pneumonia. A case report.

We compared the morphological characteristics and density properties of eosinophil leukocytes obtained from the blood and bronchoalveolar lavage fluid of a 29-year-old patient with chronic eosinophil pneumonia during exacerbation. The lavage eosinophils were significantly increased in size when compared with blood cells (surface area: 208 +/- 12 microns 2 versus 161 +/- 13 microns 2). Moreover, eosinophils contained slightly more granules (23.4 versus 20.7 per cell surface area), but no difference was found when the number was corrected for cell size. Electron microscopy revealed a loss of granule contents in eosinophils from both blood and bronchoalveolar lavage. Finally, 61% of the lavage eosinophils were hypodense (with a density less than 1.085 g/ml), whereas 96.3% of the blood cells were normodense. In conclusion, our data demonstrate that in chronic eosinophil pneumonia, eosinophils obtained from bronchoalveolar lavage and blood show differences in both their morphology and density, suggesting that eosinophils during migration into the lung may become activated.

Adult↗
PubMed1992

Cytokines, platelet activating factor and eosinophils in asthma.

Understanding of the pathogenesis of asthma has increased considerably during the past few years. These advances were possible through scientific progress in three areas which contribute to this complex and multifaceted disease: (a) the much clearer understanding of eosinophil function; (b) the defining of lipid mediators in tissue inflammation and bronchial obstruction; and (c) the growing knowledge about the biological action of a new class of protein hormones, collectively called cytokines. In line with this, evidence has accumulated of how these components may interact with each other in providing the basis of inflammatory processes in asthma. Hence it seems appropriate to review the potential implications of this new information for the pathogenesis and therapy of this disease.

Animals↗
PubMed1991

Episodic eosinophilia-myalgia-like syndrome in a patient without L-tryptophan use: association with eosinophil activation and increased serum levels of granulocyte-macrophage colony-stimulating factor.

We have studied a patient with recurrent bouts of angioedema, myalgia, and eosinophilia that was not due to L-tryptophan ingestion. Peripheral blood eosinophils (EOSs) during exacerbations of his illness displayed characteristics of "activation," including hypodense phenotype and increased responsiveness to platelet-activating factor (PAF) in vitro with respect to expression of CD11b surface adhesion proteins. Elevated serum levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) bioactivity were also detected, whereas interleukin-3 and interleukin-5 levels were not increased. During treatment with glucocorticoids, all clinical symptoms resolved, EOSs decreased in number and became normodense, PAF responsiveness diminished, and GM-CSF levels returned to normal. During glucocorticoid tapering, a subsequent clinical relapse was again associated with EOS hypodensity, increased PAF responsiveness, and increased serum GM-CSF levels. Although this patient satisfies the diagnostic criteria for eosinophilia-myalgia syndrome, the episodic and profound nature of exacerbations and response to therapy in the absence of L-tryptophan usage suggests a possible overlap with the syndrome of episodic angioedema and eosinophilia. In vitro studies suggest that GM-CSF may play a role in the eosinophilia, EOS activation, and pathophysiology of disease in this patient and demonstrate resolution of these abnormalities during glucocorticoid therapy. The efficacy of glucocorticoid therapy in some hypereosinophilic states may therefore be mediated, at least in part, via reduction of GM-CSF production and/or EOS activation.

Angioedema↗
PubMed1991

Platelet-activating factor stimulates a rapid accumulation of inositol (1,4,5)trisphosphate in guinea pig eosinophils: relationship to calcium mobilization and degranulation.

The effect of platelet-activating factor (PAF) on inositol (1,4,5)trisphosphate (Ins[1,4,5]P3) mass, calcium mobilization, and the release of granule enzymes was studied on guinea pig peritoneal eosinophils (EOSs). PAF evoked a concentration-dependent accumulation of Ins(1,4,5)P3 with a drug concentration that elicits 50% of the maximum attainable response (EC50) of 10 nmol/L; the production of this second messenger was maximal at 1 mumol/L of PAF. Kinetic analysis of PAF (1 mumol/L)-induced Ins(1,4,5)P3 accumulation demonstrated it to be transient with a 3.8-fold increase over resting levels observed at 5 seconds. Thereafter, the level of Ins(1,4,5)P3 declined, returning to vehicle-treated levels 60 seconds after PAF challenge. Lyso-PAF, the inactive precursor and metabolite of PAF, was inactive at all concentrations examined. PAF also induced a rapid, concentration-dependent (EC50, 12 nmol/L) rise in the cytosolic-free calcium concentration ([Ca++]i) in fura 2-AM-loaded EOSs that was transient, peaking after the maximum increase in Ins(1,4,5)P3 mass was observed. A highly significant positive correlation was found between the peak increase in Ins(1,4,5)P3 and the peak rise in [Ca++]i. Functionally, PAF evoked a concentration-dependent release of granule constituents from both the small (arylsulfatase B; EC50, 3 nmol/L) and specific (EOS peroxidase; EC50, 2.7 nmol/L) granules that lagged, temporally, behind both Ins(1,4,5)P3 accumulation and the rise in [Ca++]i. Both the biochemical and functional effects of PAF examined in this study were antagonized by WEB 2086 (300 nmol/L), a selective PAF receptor-blocking drug. It is concluded that stimulus (PAF)-response coupling in guinea pig peritoneal EOSs may involve the receptor-mediated formation of Ins(1,4,5)P3 and subsequent release of intracellularly stored Ca++. This sequence of events may link PAF receptor activation to Ca(++)-dependent cellular responses, such as degranulation.

Animals↗