© 1995 American Heart Association, Inc.
Articles |
Ligation of Endothelial 
vß3 Integrin Increases Capillary Hydraulic Conductivity of Rat Lung
From the Departments of Medicine (H.T., X.Y., C.F., S.I., B.A.B., J.B.), Physiology & Cellular Biophysics (J.B.), and Pediatrics (S.B.), College of Physicians & Surgeons, Columbia University, St. Luke's-Roosevelt Hospital Center, New York, NY; the Department of Physiology (P.M.-L.), Albany (NY) Medical College; and the Department of Medicine (S.A.), University of Pennsylvania School of Medicine, Philadelphia.
Correspondence to Dr. J. Bhattacharya, Columbia University, St. Luke's-Roosevelt Hospital Center, 1000 10th Ave, New York, NY 10019.
Abstract 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 
vß3.
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
vß3 integrin but not by an irrelevant
monoclonal antibody isotype matched with LM609, by a monoclonal
antibody against the vß5 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
vß3 integrin of lung capillary
endothelium increases transcapillary liquid
flux, and (2) the dominant signal transduction pathway for this effect
occurs through tyrosine kinase activation.
Key Words: endothelium • permeability • immunology • vitronectin • integrin
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