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. P ericytes in the lung circulation proliferate and contribute to the rem odeling seen in experimental sepsis. It is unknown whether endotoxin c an directly stimulate pericyte growth or induce contraction. We show t hat 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 bei ng most potent. Lipid A is the active portion of the lipopolysaccharid e, with equal activity at one-tenth the dose of lipopolysaccharide. En dotoxin's mitogenic effect requires the presence of serum, consistent with the requirement for a soluble CD14 receptor in the serum. Using F ACS analysis, the pericytes lack surface CD14 receptors. Lipopolysacch aride exposure rapidly increases intracellular calcium and induces con traction of pericytes plated onto silicone membranes. Thus, endotoxin is a direct mitogen for lung pericytes in vitro and also induces peric yte contraction. Endotoxin, present in lung tissue early during sepsis , might directly contribute to the vascular remodeling in sepsis-induc ed lung injury. (C) 1998 Academic Press.