Enhanced Tissue Expression and Elevated Circulating Level of Phospholipase A2 Receptor during Murine Endotoxic Shock

Phospholipase A2 receptor (PLA2R) mediates a variety of biological responses elicited by mammalian secretory phospholipase A2 (sPLA2). In mice, group IB sPLA2 (sPLA2-IB) acts as an endogenous ligand of PLA2R, and analysis of PLA2R-deficient mice has demonstrated a critical role of the sPLA2-IB/PLA2R system in the production of proinflammatory cytokines such as tumor necrosis factor α (TNF-α) in the development of endotoxic shock. Here, we generated specific antibodies against a recombinant soluble form of PLA2R and examined its expression in the lung and spleen where a remarkable elevation of TNF-α expression has been observed during endotoxemia. Immunohistochemical analysis revealed the expression of PLA2R in type II alveolar epithelial cells and a subset of splenic lymphocytes, and its expression levels were markedly enhanced at 1 h after endotoxin challenge. Analysis with a newly developed sandwich enzyme-linked immunosorbent assay system revealed the presence of a soluble form of PLA2R in plasma of wild-type mice compared with its absence in plasma of PLA2R-deficient mice. After exposure to endotoxin, its circulating level was significantly elevated to the maximum level at 2–3 h after the treatment. These results suggest that tissue expression and the circulating level of PLA2R are elevated during murine endotoxemia, which might be relevant to its potential roles in the production of proinflammatory mediators during the development of inflammatory conditions.