Phospholipase A2-induced rat mast cell secretion. Role of arachidonic acid metabolites.
Highly purified porcine phospholipase A2 induced noncytotoxic rat cell degranulation, as indicated by release of histamine without release of the cytoplasmic marker lactate dehydrogenase. Ultrastructural studies using transmission, scanning, and freeze fracture electron microscopic techniques indicated that phospholipase A2-induced degranulation was comparable to that caused by other mast cell secretagogues. Secretory changes noted were fusion of perigranular and plasma membranes, formation of vacuoles containing less electron-dense granules, and exocytosis of the altered granules through pores in the plasma membrane, without alteration in other intracellular organelles. The earliest consistent feature of the exocytotic process (within 1 minute) was the formation of plasma membrane bulges overlying cytoplasmic granules, with depletion of intramembranous particles from the bulges and a reduction in surface microridges. Phospholipase A2-induced mast cell degranulation was blocked by the phospholipase inhibitor 4-bromophenacyl bromide and by eicosa-5,8,11,14-tetraynoic acid (ETYA) but not by indomethacin. Since ETYA inhibits both the cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism and indomethacin only the cyclooxygenase pathway, these findings are compatible with the mediation of phospholipase A2-induced mast cell degranulation by a lipoxygenase product of the released arachidonic acid ETYA, however, may inhibit phospholipase activity directly and thus affect degranulation by phospholipase A2 in this way. These studies indicate that phospholipase A2 can induce mast cell degranulation and provides evidence that is compatible with, but not proof of, mediation of this process by a lipoxygenase product of arachidonic acid metabolism.
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D003594:Cytoplasmic Granules / Q000648:ultrastructure; D005614:Freeze Fracturing; D006632:Histamine / Q000032:analysis / Q000378:metabolism; D008084:Lipoxygenase / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D010740:Phospholipases / Q000494:pharmacology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D054467:Phospholipases A2; D051381:Rats; D011919:Rats, Inbred Strains
D001095:Arachidonic Acids; D006632:Histamine; D008084:Lipoxygenase; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2