Genetic evidence for distinct roles of COX-1 and COX-2 in the immediate and delayed phases of prostaglandin synthesis in mast cells

Activation of mast cells by aggregation of their high-affinity IgE receptor s stimulates prostaglandin (PG) D-2 synthesis and secretion. An immediate p hase of PGD(2) synthesis, complete within 30 min, is followed by a delayed, second phase of PGD(2) production that reaches a maximum 4 to 8 h after ac tivation. Activation of mast cells from COX-2 (-/-) mice stimulates the rel ease of PGD(2) during the first 30 min, whereas activation of mast cells fr om COX-1 (-/-) mice does not generate any PGD(2) in the first 2 h. On the o ther hand, COX-2 (-/-) cells do not participate in delayed phase of PGD(2) synthesis, white COX-1 (-/-) cells secrete low levels of PGD(2) between 2 a nd 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 s ynthesis is dependent on activation-induced synthesis and activity of COX-2 . (C) 1999 Academic Press.