Interactions between endothelial cells and effector cells in allergic inflammation.
The local inflammatory response that occurs after repeated exposure to allergens or during the late-phase reaction results from a complex network of interactions between inflammatory cells (mast cells, eosinophils, macrophages) and resident cells belonging to the lung structure itself like EC, fibroblasts, or bronchial epithelial cells. Among structural cells, EC represent critical elements: they control leukocyte traffic through the expression of adhesion molecules; they are also able to amplify leukocyte activation through the production of proinflammatory cytokines like IL-1, IL-6, or of chemokines like IL-8. Three cell models have been successively considered. When supernatants of alveolar macrophages, recovered from patients exhibiting a late asthmatic response after allergen exposure, were tested on HUVEC cultures, a TNF alpha-dependent ICAM-1 and E-selectin overexpression was observed. Among mast-cell mediators, histamine was already known to induce a rapid and transient expression of P-selectin; we demonstrated that histamine also induced an IL-6 and IL-8 secretion by HUVEC, which was concentration-dependent and inhibited by H1 or H2 receptor antagonists. Finally purified eosinophils obtained from donors with hypereosinophilia similarly increased adhesion molecule expression and chemokine production. The precise nature of the eosinophil product(s) involved in this process is currently under investigation.
Tonnel
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Unité INSERM n degree 416, Institut Pasteur Lille, France.
Gosset
P
P
Molet
S
S
Tillie-Leblond
I
I
Jeannin
P
P
Joseph
M
M
D001249:Asthma / Q000473:pathology; D001980:Bronchi / Q000098:blood supply; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002450:Cell Communication; D004730:Endothelium, Vascular / Q000166:cytology* / Q000276:immunology; D004804:Eosinophils / Q000166:cytology* / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000473:pathology*; D016209:Interleukin-8 / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000166:cytology / Q000276:immunology; D008407:Mast Cells / Q000166:cytology / Q000276:immunology; D008833:Microcirculation; D008954:Models, Biological; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha