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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 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 activat...

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Published in:Biochemical and biophysical research communications 1999-11, Vol.265 (1), p.205-210
Main Authors: Reddy, Srinivasa T., Tiano, Howard F., Langenbach, Robert, Morham, Scott G., Herschman, Harvey R.
Format: Article
Language:English
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Summary: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.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.1999.1658