Endothelial leukocyte adhesion molecule-1 and intercellular adhesion molecule-1 mediate the adhesion of eosinophils to endothelial cells in vitro and are expressed by endothelium in allergic cutaneous inflammation in vivo.
We have compared the adhesion of 51Cr-labeled eosinophils and neutrophils to cultured human umbilical vein endothelial cell (EC) monolayers that have been stimulated with IL-1, TNF, or LPS. Each agent stimulated the adhesion to EC of both eosinophils and neutrophils in a similar dose- and time-dependent manner. F(ab')2 fragments of mAb 1.2B6 (anti-endothelial leukocyte adhesion molecule (ELAM)-1) and mAb 6.5B5 (anti-intercellular adhesion molecule (ICAM)-1) each inhibited partially, and to a similar extent, eosinophil and neutrophil adhesion to EC monolayers prestimulated with TNF (10 ng/ml) for 6 h. Greater inhibition of both eosinophil and neutrophil adhesion was achieved by combining the effects of mAb 1.2B6 with either mAb 6.5B5 or mAb TS1/18 (anti-CD18). These observations indicate that both ELAM-1 and ICAM-1 are involved in the adhesion of eosinophils and neutrophils to EC stimulated with TNF. In order to determine whether these molecules are expressed in vivo during allergen-induced late phase allergic responses in the skin, human skin biopsies were examined at 6 h after Ag or saline challenge with the use of an alkaline phosphatase-staining technique. Both ELAM-1 and ICAM-1 were expressed with greater intensities in Ag-challenged biopsies, suggesting that these molecules may be involved in granulocyte recruitment in vivo. The similarities we have established between mechanisms of eosinophil and neutrophil adhesion to cytokine-stimulated EC suggests that factors other than differential leukocyte-EC adhesion may be responsible for the selective accumulation of eosinophils at sites of allergic inflammation.
Department of Allergy, United Medical School, Guy's Hospital, London, U.K.
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U
Kyan-Aung
D O
DO
Haskard
R N
RN
Poston
M H
MH
Thornhill
T H
TH
Lee
D000328:Adult; D000911:Antibodies, Monoclonal; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D003872:Dermatitis / Q000276:immunology*; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D004804:Eosinophils / Q000502:physiology*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1; D007376:Interleukin-2 / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology; D012867:Skin / Q000098:blood supply; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D007376:Interleukin-2; D008070:Lipopolysaccharides; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1