DIFFERENTIAL REGULATION OF ELICITED-PERITONEAL MACROPHAGE 14 KDA AND 85 KDA PHOSPHOLIPASE A(2)(S) BY TRANSFORMING GROWTH-FACTOR-BETA

Elicited guinea pig macrophages collected from inflammatory peritoneal exudate release soluble 14 kDa phospholipase A(2) (PLA(2)) and prostaglandin E(2) (PGE(2)) into surrounding media during culture (Marshall et al. (1994) J. Lipid Med. 10, 295-313). The effect of transformation growth factor beta(1) (TGF beta), an immunoregulatory growth factor, was examined in this system. Exposure of cultured macrophages to TGF beta reduced both the activity and protein levels of 14 kDa PLA(2) measured in conditioned media. This inhibition occurred within the first 6-8 h, was prevalent through 72 h of exposure and was dependent on TGF beta concentration. The reduction, however, never reached more than 40-60%. Evaluation of the cellular PLA(2) activity confirmed the existence of an immunologically-related 14 kDa PLA(2) (ELISA) in the particulate fraction and an 85 kDa PLA(2) (Western analysis) in the cytosol. Exposure to TGF beta halved the particulate activity and protein levels of 14 kDa PLA(2) which was consistent with the reduction in the secreted form. Alternatively, TGF beta induced an increase in cytosolic 85 kDa PLA(2) (activity and protein) which was not apparent until 12 h and significant at 20-24 h of exposure. This demonstrates that TGF beta differentially regulates the production of these two enzymes. Despite this, neither PGE(2) synthesis nor the up-regulated cyclooxygenase -II were altered by TGF beta treatment suggesting that maximal prostanoid synthesis had been reached.