Secretory type II phospholipase A2 and the generation of intrauterine signals

Abstract

Recent advances in the understanding of the metabolism of cell membrane glycerophospholipids and the subsequent generation of biologically active metabolites have provided new insight into their role in normal spontaneous-onset labour and delivery at term, and in preterm labour. In particular, multiple isozymes of the lipolytic enzyme phospholipase A2 (PLA2) have been identified in human gestational tissue during late pregnancy and at the time of labour. Specific isozymes have been identified that are active intracellularly (e.g. cytosolic PLA2) or extracellularly (e.g. Type II and Type IV secretory PLA2). The relative contribution of these isozymes to total PLA2 activity is tissue specific and affected by labour status. The development of isozyme-specific inhibitors of PLA2 may afford the opportunity to better regulate the formation of biologically active phospholipid metabolites within intrauterine compartments. With the identification of secretory PLA2 isozymes in human gestational tissues, a new pathway for materno-fetal and/or intrauterine communication has been established--a pathway in which secretory PLA2 isozymes released by intrauterine tissues act in an autocrine, paracrine or even endocrine fashion to affect glycerophospholipid metabolism, cell membrane fluidity and the generation of biological mediators.