Macrophages activated by fibrin increase albumin permeability across pulmonary artery endothelial monolayers.
We have examined the effects of alveolar macrophages (AM) obtained after challenge with alpha-thrombin on 125I-labeled albumin permeability across ovine pulmonary artery endothelial monolayers. AM were obtained by bronchoalveolar lavage before and after challenging the sheep with alpha-thrombin (80 U/kg). Post-thrombin AM increased 125I-labeled albumin transendothelial permeability, whereas resting AM had no effect (82.7 +/- 7.9% increase versus 17.2 +/- 1.6% increase at the AM:endothelial cell ratio of 1:1; p less than 0.001). The permeability increase was also seen at AM:endothelial cell ratios of 0.2:1 and 5:1. Endothelial permeability to 125I-labeled albumin did not increase after in vitro incubation of macrophages with 10(-8) M thrombin, suggesting that AM are activated as a result of thrombin-induced fibrin microembolism rather than by the alpha-thrombin per se. The increase in permeability was not due to endothelial lysis since macrophages did not cause release of endothelial lactate dehydrogenase. Adherence of AM to the endothelium did not correlate with the ability of AM to increase endothelial permeability. Superoxide anion production was increased when post-thrombin AM were exposed to the endothelial monolayers (30.6 +/- 4.2 nmol/10(6) cells/10 min) compared with production by post-thrombin AM in the absence of endothelial cells (2.5 +/- 0.5 nmol/10(6) cells/10 min). The addition of superoxide dismutase (SOD) blunted the permeability increase induced by AM (32.3 +/- 3.9% increase with SOD versus 84.1 +/- 7.1% increase without SOD; p less than 0.001), indicating that superoxide anion is an important mediator of the macrophage-induced increase in endothelial monolayer permeability.(ABSTRACT TRUNCATED AT 250 WORDS)
Ferro
T J
TJ
Department of Physiology, Albany Medical College of Union University, New York.
Lynch
J J
JJ
Malik
A B
AB
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002199:Capillary Permeability; D004730:Endothelium, Vascular / Q000502:physiology*; D005337:Fibrin / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D008262:Macrophage Activation; D008264:Macrophages / Q000502:physiology*; D008297:Male; D011650:Pulmonary Alveoli / Q000166:cytology; D011651:Pulmonary Artery / Q000502:physiology; D012756:Sheep; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
D007457:Iodine Radioisotopes; D013481:Superoxides; D005337:Fibrin; D013482:Superoxide Dismutase; D013917:Thrombin