Genetic Evidence for Distinct Roles of COX-1 and COX-2 in the Immediate and Delayed Phases of Prostaglandin Synthesis in Mast Cells

Abstract

Activation of mast cells by aggregation of their high-affinity IgE receptors stimulates prostaglandin (PG) D2 synthesis and secretion. An immediate phase of PGD2 synthesis, complete within 30 min, is followed by a delayed, second phase of PGD2 production that reaches a maximum 4 to 8 h after activation. Activation of mast cells from COX-2 (−/−) mice stimulates the release of PGD2 during the first 30 min, whereas activation of mast cells from COX-1 (−/−) mice does not generate any PGD2 in the first 2 h. On the other hand, COX-2 (−/−) cells do not participate in delayed phase of PGD2 synthesis, while COX-1 (−/−) cells secrete low levels of PGD2 between 2 and 4 h after activation. These data demonstrate that (i) the first phase of PG synthesis is COX-1 dependent and (ii) the second, delayed phase of PG synthesis is dependent on activation-induced synthesis and activity of COX-2.