Keratinocytes-associated chemokines and enzymatically quiescent heparanase induce the binding of resting CD4+ T cells

Rami Hershkoviz, Moshe Marikovsky, Dalia Gilat, Ofer Lider

Research output: Contribution to journalArticlepeer-review

Abstract

Whether the chemokines macrophage inflammatory protein-1β (MIP-1β) and regulated on activation normal T expressed and secreted (RANTES), which interact specifically with glycosaminoglycans and thus mediate the recruitement, attachment, and migration of leukocytes to vascular endothelia and extracellular matrix, are also involved in interactions between CD4+ murine T lymphocytes and keratinocytes was examine. We have previously observed that depending on the local pH, a mammalian extracellular matrix-degrading enzyme, endo-β-D glucuronidase (heparanase), which cleaves heparan sulfate proteoglycans, can function either 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°C and pH 7.2, radioactively labeled MIP-1β, RANTES, and heparanase bound to confluent layers of resting keratinocyte 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-1β, RANTES, and the enzymatically quiescent heparanase to keratinocyte. These results suggest that certain chemokines and heparanase may function to restrict passing leukocytes, notably 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.

Original languageEnglish
Pages (from-to)243-248
Number of pages6
JournalJournal of Investigative Dermatology
Volume106
Issue number2
DOIs
StatePublished - 1996
Externally publishedYes

Keywords

  • Heparan-sulfate
  • Inflammation
  • MIP-1β
  • RANTES
  • T lymphocytes

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