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) D(2) synthesis and secretion. An immediate phase 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 activation. Activation of mast cells from COX-2 (-/-) mice stimulates the release of PGD(2) during the first 30 min, whereas activation of mast cells from COX-1 (-/-) mice does not generate any PGD(2) in the first 2 h. On the other hand, COX-2 (-/-) cells do not participate in delayed phase of PGD(2) synthesis, while COX-1 (-/-) cells secrete low levels of PGD(2) 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.
Reddy
S T
ST
Molecular Biology Institute, University of California-Los Angeles Center for the Health Sciences, Los Angeles, California, 90095, USA.
Tiano
H F
HF
Langenbach
R
R
Morham
S G
SG
Herschman
H R
HR
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002460:Cell Line; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D007700:Kinetics; D008407:Mast Cells / Q000201:enzymology / Q000502:physiology*; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D015230:Prostaglandin D2 / Q000096:biosynthesis; D011451:Prostaglandin-Endoperoxide Synthases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis*; D013997:Time Factors
D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D015230:Prostaglandin D2