Regulation of prostaglandin F2alpha by the specific inhibition of secretory type II phospholipase A2: implications for the management of premature labour.
Arachidonic acid mobilisation by phospholipase A2 (PLA2) and subsequent prostaglandin synthesis is thought to be a pivotal event in the onset and/or maintenance of human labour. The purpose of this study was to examine the efficacy of a monoclonal human type II PLA2 antibody (10 B2) in reducing prostaglandin F2alpha (PGF2alpha) production in Chinese hamster ovary (CHO) cells (that overexpress human recombinant type II PLA2) and in human placental explants. 10 B2 caused a concentration-dependent inhibition of PLA2 activity (p < 0.00001) and PGF2alpha release (p < 0.01) by CHO cells. 1 microM of 10 B2 inhibited PLA2 activity (p < 0.00001) and PGF2alpha production (p < 0.0001) in human placental explants. The latter effect was significantly reversed by the addition of arachidonic acid (30 microM; p < 0.01). On the basis of these findings, it is proposed that 10 B2 inhibits PGF2alpha production by interfering with the extracellular activity of type II PLA2.
Perinatal Research Centre, Royal Women's Hospital, Carlton, Vic., Australia.
M J
MJ
Munns
R G
RG
King
G E
GE
Rice
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D016718:Arachidonic Acid / Q000494:pharmacology; D016466:CHO Cells / Q000378:metabolism; D006224:Cricetinae; D015237:Dinoprost / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007752:Obstetric Labor, Premature / Q000628:therapy*; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000235:genetics; D054467:Phospholipases A2; D010920:Placenta / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D011247:Pregnancy
D000911:Antibodies, Monoclonal; D004791:Enzyme Inhibitors; D016718:Arachidonic Acid; D015237:Dinoprost; D010741:Phospholipases A; D054467:Phospholipases A2