Effects of endotoxin on lung pericytes in vitro.
Lipopolysaccharide released during bacterial sepsis causes acute lung injury and ARDS. Pulmonary microvascular injury is a feature of ARDS, and vascular remodeling develops, leading to pulmonary hypertension. Pericytes in the lung circulation proliferate and contribute to the remodeling seen in experimental sepsis. It is unknown whether endotoxin can directly stimulate pericyte growth or induce contraction. We show that lipopolysaccharide from Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae increases rat lung pericyte proliferation in vitro by up to 72% on day 7 of exposure (P < 0.001), with E. coli being most potent. Lipid A is the active portion of the lipopolysaccharide, with equal activity at one-tenth the dose of lipopolysaccharide. Endotoxin's mitogenic effect requires the presence of serum, consistent with the requirement for a soluble CD14 receptor in the serum. Using FACS analysis, the pericytes lack surface CD14 receptors. Lipopolysaccharide exposure rapidly increases intracellular calcium and induces contraction of pericytes plated onto silicone membranes. Thus, endotoxin is a direct mitogen for lung pericytes in vitro and also induces pericyte contraction. Endotoxin, present in lung tissue early during sepsis, might directly contribute to the vascular remodeling in sepsis-induced lung injury.
Sir Mortimer B. Davis Jewish General Hospital, McGill University, Montreal, Quebec, H3T 1E2, Canada.
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Khoury
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Langleben
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004926:Escherichia coli; D007711:Klebsiella pneumoniae; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000166:cytology*; D008297:Male; D020286:Pericytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011550:Pseudomonas aeruginosa; D051381:Rats; D017207:Rats, Sprague-Dawley
D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides