STIMULATION OF MATRIX METALLOPROTEINASE-DEPENDENT MIGRATION OF T-CELLS BY EICOSANOIDS

Prostaglandin E(2) (PGE(2)) and leukotriene B4 (LTB4), at nanomolar to micromolar concentrations, elicited migration of human blood T cells and cultured T lymphoblastoma cells of the Tsup-1 line through a layer of Matrigel basement membrane matrix, The density of Tsup-1 cell high -affinity receptors was low for PGE(2) and high for LTB4, resulting in respectively predominant chemokinetic and chemotactic: stimulation of migration, Migration-enhancing concentrations of PGE(2) and LTB4 also increased Tsup-1 cell content and secretion of matrix metalloproteina ses (MMPs) 2, 3, and 9, which were quantified by Western blots and zym ography, and augmented Tsup-1 cell-surface expression of the MMPs, as shown by flow cytometry, That a specific MMP inhibitor suppressed migr ation of blood T cells and Tsup-1 cells through Matrigel, but did not affect PGE(2)- and LTB4-initiated T cell migration through micropore f ilters without Matrigel, suggests dual requirements for MMP expression and enhanced motility in T cell passage through basement membranes.