Degranulation of human mast cells induces an endothelial antigen central to leukocyte adhesion.

Abstract

To understand better the role of mast cell secretory products in the genesis of inflammation, a system was developed for in vitro degranulation of human mast cells in skin organ cultures. Within 2 hr after morphine sulfate-induced degranulation, endothelial cells lining microvessels adjacent to affected mast cells expressed an activation antigen important for endothelial-leukocyte adhesion. Identical results were obtained when other mast cell secretagogues (anti-IgE, compound 48/80, and calcium ionophore A23187) were used. Induction of this antigen was abrogated by preincubation with cromolyn sodium, an inhibitor of mast cell secretion, and by antiserum to tumor necrosis factor a. These findings indicate that de-

Macrophage Migration Inhibitory Factor Increases Leukocyte–Endothelial Interactions in Human Endothelial Cells via Promotion of Expression of Adhesion Molecules

“…The reasons underlying these differences in reported responses to MIF treatment are unclear, although it is conceivable that they stem from functional differences in endothelial cells from different vascular sites. In vivo studies have established that endothelial cells from arterial and venous sources have differing capacities in terms of adhesion molecule expression (49)(50)(51)(52). Studies in which MIF treatment was found to induce mononuclear leukocyte arrest were performed using aortic endothelial cells, whereas the present studies used endothelial cells derived from umbilical veins (26).…”

Modulation of adhesion molecule expression on endothelial cells during the late asthmatic reaction: role of macrophage-derived tumour necrosis factor-alpha

“…anti-lgE or compound 48/SO. and correlated with ma.st ceil degranulation [10,14]. ELAM-I expression appears to be TNF-dependent and can be inhibited by prior incubation wilh cromolyn.…”

“…ELAM-I expression appears to be TNF-dependent and can be inhibited by prior incubation wilh cromolyn. a drug able to prevent mast cell degranulation [10]. In a recent report, Walsh f/«/, demonstrated thai mast cells were the main source of TNF in normal human dermis, and that iheir degranulation released TNF.…”

“…It was shown that endothelial-leucocyte adhesion molecule-1 (ELAM-I) and intercellular adhesion molecule-1 (ICAM-1) were strongly increased on endolhelial cells following an experimental allergen challenge [10][11][12], and in allergic cutaneous inflammation [13,14J, Furthermore, trealmenl with anti-ICAM-I MoAbs has been shown to decrease eosinophil infiltration and bronchial hyperreactivity in an animal model of aslhma [II]. These results indicate thai vascular endothelial cell expression of ICAM-l, which mediates LFA-1-dependent adherence of leucocytes, in particular of eosinophils.…”

Enhanced Allergic Sensitization in Animals Exposed to Particulate Air Pollution

“…IL-6 stimulates the polarization of naive T cells (Th0 cells) to Th2 cells via induction of IL-4 gene expression (Rincon et al, 1997) and in uences IgE synthesis (Vercelli et al, 1989). TNF-a stimulates B lymphocyte activity (Kehrl et al, 1987) and is increased in the lungs of asthmatics (Casale et al, 1996), where it facilitates extravasation of leukocytes into the tissue via upregulation of vascular cell adhesion molecule 1 (VCAM-1) (Klein et al, 1989;Moser et al, 1992). In addition to the activation processes just described, pulmonary in ammation also features edema from epithelial damage, which may result in a loss of barrier function and enhanced translocation of inhaled antigen to the submucosa (Matsamura, 1970).…”