Inhibition of the transendothelial migration of human T lymphocytes by prostaglandin E2.
To determine whether part of the anti-inflammatory effects of prostaglandin E2 (PGE2) was related to inhibition of T cell interactions with endothelial cells (EC), the effects of PGE2 and other cAMP-elevating agents on the transendothelial migration of human T cells was examined. Although PGE2 did not effect T cell binding to EC, concentration-dependent inhibition of the transendothelial migration of T cells through unstimulated or IL-1-activated EC was observed. PGE2 inhibited the function of both T cells and EC, with maximal inhibition observed when both T cells and EC were treated with PGE2. However, the inhibitory action of PGE2 could not be ascribed to an effect on the adhesion receptor pair, CD11a/CD18-CD54. The inhibitory effect of PGE2 seemed to relate to its capacity to elevate cellular cAMP levels, because 3-isobutyl-1-methylxanthine enhanced PGE2 activity and dibutyryl cAMP and forskolin also inhibited transendothelial migration. The inhibitory effect of PGE2 and the other cAMP-elevating agents on the function of T cells related in part to suppression of their intrinsic locomotory behavior as random migration in the absence of EC was blocked. In EC, PGE2 and the other cAMP-elevating agents increased the barrier function of EC as evidenced by a decrease in the diffusion of [3H]mannitol through the endothelium. These results indicate that part of the anti-inflammatory action of PGE2 relates to its capacity to suppress the transendothelial migration of T cells by cAMP-mediated alterations in the function of both T cells and EC.
Oppenheimer-Marks
N
N
Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center, Dallas 75235.
Kavanaugh
A F
AF
Lipsky
P E
PE
D003994:Bucladesine / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004058:Diffusion; D015232:Dinoprostone / Q000494:pharmacology* / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000503:physiopathology; D016023:Integrins / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008353:Mannitol / Q000493:pharmacokinetics; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000502:physiology
D016023:Integrins; D007375:Interleukin-1; D005576:Colforsin; D008353:Mannitol; D003994:Bucladesine; D000242:Cyclic AMP; D015232:Dinoprostone