Expression of prostaglandin G/H synthase (cyclooxygenase) during murine fetal thymic development.
Fetal thymic lobes in organ culture have been shown to have the capacity to metabolize [14C]arachidonic acid (AA) to prostaglandins (PGs), including 6-ketoPGF1 alpha, PGF2 alpha, PGE2, and PGA2. Inhibition of AA metabolism results in inhibition of growth and Thy 1 expression during thymic organ culture. We report herein that freshly-isolated fetal thymic lobes also have the capacity to metabolize [14C]AA to PGs and HETEs at Days 14 and 16 of prenatal murine development. RNA encoding phospholipase A2, which liberates arachidonic acid from membrane phospholipids, and cyclooxygenase (prostaglandin G/H synthase), the first enzyme involved in the conversion of AA to PGs, are expressed during thymic development. We have localized the cyclooxygenase protein to stromal cells in the fetal and adult thymus. Exogenous AA or an analogue of PGI2 (iloprost) stimulated growth of fetal thymocytes in organ culture. These findings, together with our studies of the morphology of thymic lobes cultured with inhibitors of arachidonate metabolism, support the hypothesis that PGs are required for thymocyte proliferation during thymic development.
Appasamy
P M
PM
Pittsburgh Cancer Institute, Pennsylvania.
Pendino
K
K
Schmidt
R R
RR
Chepenik
K P
KP
Prystowsky
M B
MB
Goldowitz
D
D
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D015232:Dinoprostone / Q000494:pharmacology; D015870:Gene Expression; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D016285:Iloprost / Q000494:pharmacology; D007150:Immunohistochemistry; D007213:Indomethacin / Q000494:pharmacology; D051379:Mice; D008808:Mice, Inbred CBA; D009924:Organ Culture Techniques; D010741:Phospholipases A / Q000235:genetics / Q000378:metabolism; D054467:Phospholipases A2; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D013950:Thymus Gland / Q000196:embryology* / Q000201:enzymology
D001095:Arachidonic Acids; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D016718:Arachidonic Acid; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054467:Phospholipases A2; D016285:Iloprost; D015232:Dinoprostone; D007213:Indomethacin