Inhibition of the transendothelial migration of human T lymphocytes by prostaglandin E2
Oppenheimer-Marks, N.; Kavanaugh, A.F.; Lipsky, P.E.
Journal of Immunology 152(12): 5703-5713
1994
ISSN/ISBN: 0022-1767 PMID: 8207201 Document Number: 430287
To determine whether part of the anti-inflammatory effects of prostaglandin E-2 (PGE-2) was related to inhibition of T cell interactions with endothelial cells (EC), the effects of PGE-2 and other cAMP-elevating agents on the transendothelial migration of human T cells was examined. Although PGE-2 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. PGE-2 inhibited the function of both T cells and EC, with maximal inhibition observed when both T cells and EC were treated with PGE-2. However, the inhibitory action of PGE-2 could not be ascribed to an effect on the adhesion receptor pair, CD11a/CD18-CD54. The inhibitory effect of PGE-2 seemed to relate to its capacity to elevate cellular cAMP levels, because 3-isobutyl-1-methylxanthine enhanced PGE-2 activity and dibutyryl cAMP and forskolin also inhibited transendothelial migration. The inhibitory effect of PGE-2 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, PGE-2 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 antiinflammatory action of PGE-2 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.