Soluble complex of complement increases hydraulic conductivity in single microvessels of rat lung.
We determined the effect of sera enriched with the soluble complex of complement (SC5b-9), on hydraulic conductivity (Lp) of single pulmonary venules (diameter 20-30 microns). Sera free of anticoagulants and blood cells were prepared from rat and human blood. Lp were determined by our split drop technique in isolated, blood-perfused lungs prepared from anesthetized rats (2% halothane; Sprague Dawley, 500 g; n = 73). Zymosan-activated (ZAS) and control sera were used for Lp determinations. In ZAS prepared from human serum, SC5b-9 concentration was > 300 micrograms/ml (control: < 1 microgram/ml) as determined by ELISA. At baseline, Lp averaged 3.4 +/- .4 x 10(-7) ml/(cm2.s.cm H2O), but it increased by 217 +/- 32% with undiluted ZAS (P < 0.05). The Lp increase correlated significantly with different ZAS dilutions for rat serum and with SC5b-9 concentration for human serum. Lp did not increase significantly with ZAS prepared from heat-treated sera, C6- and C8-deficient sera; or with ZAS in which SC5b-9 had been depleted by immunoprecipitation. The ZAS-induced increase of Lp was blocked completely by venular preinfusion with the arginine-glycine-aspartic acid (RGD) tripeptide (1 mg/ml, 10 min). We report for the first time that: (a) SC5b-9 increases lung endothelial Lp; and (b) the increase of Lp is attributable to an integrin-dependent mechanism.
Ishikawa
S
S
Department of Medicine, College of Physicians and Surgeons, Columbia University, St. Luke's-Roosevelt Hospital Center, New York 10019.
Tsukada
H
H
Bhattacharya
J
J
D000818:Animals; D003167:Complement Activation; D003183:Complement C6 / Q000502:physiology; D003185:Complement C8 / Q000502:physiology; D015938:Complement Membrane Attack Complex / Q000494:pharmacology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology; D010477:Perfusion; D011652:Pulmonary Circulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014699:Venules / Q000187:drug effects / Q000502:physiology*; D015054:Zymosan / Q000494:pharmacology
D003183:Complement C6; D003185:Complement C8; D015938:Complement Membrane Attack Complex; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D015054:Zymosan