Ligation of endothelial alpha v beta 3 integrin increases capillary hydraulic conductivity of rat lung

Complement-mediated pulmonary edema results from increases in lung capillary hydraulic conductivity (Lp), possibly by receptor-mediated mechanisms. We considered the Lp effects of vitronectin and the vitronectin-containing complement complex SC5b-9, which ligate the integrin alpha v beta 3. Vitronec...

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Bibliographic Details
Published in:Circulation research 1995-10, Vol.77 (4), p.651-659
Main Authors: Tsukada, H, Ying, X, Fu, C, Ishikawa, S, McKeown-Longo, P, Albelda, S, Bhattacharya, S, Bray, B A, Bhattacharya, J
Format: Article
Language:English
Subjects:
Animals
Capillary Permeability
Complement Membrane Attack Complex
Complement System Proteins - pharmacology
Endothelium, Vascular - physiology
Glycoproteins - pharmacology
Lung - blood supply
Microcirculation - physiology
Rabbits
Rats
Receptors, Vitronectin - physiology
Vitronectin - pharmacokinetics
Vitronectin - physiology
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Summary:Complement-mediated pulmonary edema results from increases in lung capillary hydraulic conductivity (Lp), possibly by receptor-mediated mechanisms. We considered the Lp effects of vitronectin and the vitronectin-containing complement complex SC5b-9, which ligate the integrin alpha v beta 3. Vitronectin, SC5b-9, and SC5b-9-enriched zymosan-activated serum all rapidly increased Lp, as determined by the split-drop technique in single lung capillaries of rat lung. The Lp increases were inhibited by a monospecific (LM609) and a polyclonal (R838) antibody against the alpha v beta 3 integrin but not by an irrelevant monoclonal antibody isotype matched with LM609, by a monoclonal antibody against the alpha v beta 5 integrin, or by preimmune rabbit serum. Vitronectin monomers failed to increase Lp. The tyrosine kinase blockers genistein and methyl 2,5-dihydroxycinnamate caused significant concentration-dependent inhibitions of Lp increases due to vitronectin and zymosan-activated serum. By contrast, the protein kinase C blocker calphostin C had no major effect. We conclude that (1) multivalent ligation of the luminally located alpha v beta 3 integrin of lung capillary endothelium increases transcapillary liquid flux, and (2) the dominant signal transduction pathway for this effect occurs through tyrosine kinase activation.
ISSN:0009-7330
1524-4571
DOI:10.1161/01.RES.77.4.651