CD31-triggered rearrangement of the actin cytoskeleton in human natural killer cells

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Abstract

In this report, we analyze whether CD31, also known as platelet-endothelial cell adhesion molecule-1 (PECAM-1), can transduce an outside-in signal in human natural killer (NK) lymphocytes in vitro. We show that CD31, but not HLA class-I cross-linking triggers an outside-in transmembrane signal in NK lymphocytes, mediating cell spreading and cytoskeletal rearrangement. These phenomena are Mg 2+, but not Ca 2+ dependent, suggesting that signal transduction elicited by CD31 cross-linking may involve an associated integrin. Two possible candidates would be αv and αL, whose function is known to depend on Mg 2+. However, the CD31-induced cytoskeletal rearrangement was not reduced by the use of αv- or αL-specific F(ab') 2, suggesting that CD31 could transduce a signal by itself or by association with a still-undefined integrin. Moreover, talin, but not vinculin or tubulin, appears to co-localize with actin microfilaments in the membrane ruffles of NK cells that undergo cytoskeleton rearrangement following CD31 cross-linking. Both spreading and cytoskeletal rearrangement appear to be regulated by intracellular cyclic-3',5'-adenosine monophosphate (cAMP). Indeed, the activator of the adenylyl cyclase, forskolin, inhibited cell spreading and cytoskeletal rearrangement induced by CD31 cross-linking. This phenomenon was also observed using the membrane-permeants cAMP analog Sp adenosine-3',5'-cyclic monophosphothioate (Sp-cAMPS), but not its inactive isomer Rp-cAMPS. Likewise, adhesion of NK lymphocytes to NIH/3T3 murine fibroblasts transfected with the cDNA encoding human CD31 was blocked by increasing intracellular cAMP levels. We suggest that intracellular cAMP may be involved in CD31-mediated signal transduction, and may regulate NK-endothelial cell adhesion and possibly, the tissue localization of NK cells.

Original languageEnglish
Pages (from-to)817-824
Number of pages8
JournalEuropean Journal of Immunology
Volume26
Issue number4
DOIs
Publication statusPublished - Apr 1996

Keywords

  • cAMP
  • CD31
  • Cytoskeleton
  • Natural killer lymphocyte
  • Signal transduction

ASJC Scopus subject areas

  • Immunology

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