Enhanced tissue expression and elevated circulating level of phospholipaseA(2) receptor during murine endotoxic shock

Phospholipase A(2) receptor (PLA(2)R) mediates a variety of biological resp onses elicited by mammalian secretory phospholipase A(2) (sPLA(2)). In mice , group IB sPLA(2) (sPLA(2)-IB) acts as an endogenous ligand of PLA(2)R, an d analysis of PLA(2)R-deficient mice has demonstrated a critical role of th e sPLA(2)-IB/PLA(2)R system in the production of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) in the development of endot oxic shock. Here, we generated specific antibodies against a recombinant so luble form of PLA(2)R and examined its expression in the lung and spleen wh ere a remarkable elevation of TNF-alpha expression has been observed during endotoxemia. Immunohistochemical analysis revealed the expression of PLA(2 )R in type II alveolar epithelial cells and a subset of splenic lymphocytes , and its expression levels were markedly enhanced at 1 h after endotoxin c hallenge. Analysis with a newly developed sandwich enzyme-linked immunosorb ent assay system revealed the presence of a soluble form of PLA(2)R in plas ma of wild-type mice compared with its absence in plasma of PLA(2)R-deficie nt mice. After exposure to endotoxin, its circulating level was significant ly elevated to the maximum level at 2-3 h after the treatment. These result s suggest that tissue expression and the circulating level of PLA(2)R are e levated during murine endotoxemia, which might be relevant to its potential roles in the production of proinflammatory mediators during the developmen t of inflammatory conditions. (C) 2000 Academic Press.