Stimulation of matrix metalloproteinase-dependent migration of T cells by eicosanoids.
Prostaglandin E2 (PGE2) 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 PGE2 and high for LTB4, resulting in respectively predominant chemokinetic and chemotactic stimulation of migration. Migration-enhancing concentrations of PGE2 and LTB4 also increased Tsup-1 cell content and secretion of matrix metalloproteinases (MMPs) 2, 3, and 9, which were quantified by Western blots and zymography, and augmented Tsup-1 cell-surface expression of the MMPs, as shown by flow cytometry. That a specific MMP inhibitor suppressed migration of blood T cells and Tsup-1 cells through Matrigel, but did not affect PGE2- and LTB4-initiated T cell migration through micropore filters without Matrigel, suggests dual requirements for MMP expression and enhanced motility in T cell passage through basement membranes.
Leppert
D
D
Department of Neurology, University of California Medical Center, San Francisco 94143-0711, USA.
Hauser
S L
SL
Kishiyama
J L
JL
An
S
S
Zeng
L
L
Goetzl
E J
EJ
D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D017364:Collagenases / Q000378:metabolism* / Q000502:physiology; D015232:Dinoprostone / Q000494:pharmacology*; D018093:Gelatinases / Q000502:physiology; D006801:Humans; D007975:Leukotriene B4 / Q000494:pharmacology*; D020781:Matrix Metalloproteinase 1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000502:physiology; D018102:Receptors, Leukotriene B4 / Q000032:analysis; D018078:Receptors, Prostaglandin E / Q000032:analysis; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology
D018102:Receptors, Leukotriene B4; D018078:Receptors, Prostaglandin E; D007975:Leukotriene B4; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1; D015232:Dinoprostone