Keratinocytes-associated chemokines and enzymatically quiescent heparanase induce the binding of resting CD4+ T cells.
Whether the chemokines macrophage inflammatory protein-1 beta (MIP-1 beta) and regulated on activation normal T expressed and secreted (RANTES), which interact specifically with glycosaminoglycans and thus mediate the recruitment, attachment, and migration of leukocytes to vascular endothelia and extracellular matrix, are also involved in interactions between CD4+ murine T lymphocytes and keratinocytes was examined. We have previously observed that depending on the local pH, a mammalian extracellular matrix-degrading enzyme, endo-beta-D glucuronidase (heparanase), which cleaves heparin sulfate proteoglycans, can function wither as an enzyme or as an adhesion molecule for CD4+ T lymphocytes. Herein, the involvement of heparanase in T cell-keratinocyte interactions was also probed. At 37 degree C and pH 7.2, radioactively labeled MIP-1 beta, RANTES, and heparanase bound to confluent layers of resting keratinocytes in a saturable and an heparan sulfate- or heparin-dependent manner, and thereby induced the adhesion of resting CD4+ T cells to keratinocytes. At a relatively acidic pH characteristic of inflammatory milieu, enzymatically active heparanase did not bind to the keratinocytes but, rather, inhibited the binding of MIP-1beta, RANTES, and the enzymatically quiescent heparanase to keratinocytes. These results suggest that certain chemokines and heparanase may function to restrict passing leukocytes, notable T lymphocytes, in the cutaneous micro-environment, a site which is continuously challenged with antigens. These keratinocyte-bound lymphocytes can serve as a reservoir of immediate responders to immunological stimuli.
Hershkoviz
R
R
Department of Cell Biology, The Weizmann Institute of Science, Rehovot Israel.
Marikovsky
M
M
Gilat
D
D
Lider
O
O
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000494:pharmacology; D018925:Chemokines / Q000494:pharmacology*; D005260:Female; D005966:Glucuronidase; D006026:Glycoside Hydrolases / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology; D006497:Heparan Sulfate / Q000494:pharmacology; D006801:Humans; D015603:Keratinocytes / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D015846:Monokines / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D000099175:Heparanase
D054407:Chemokine CCL4; D018946:Chemokine CCL5; D018925:Chemokines; D005966:Glucuronidase; D006026:Glycoside Hydrolases; D006493:Heparin; D006497:Heparan Sulfate; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D000099175:Heparanase