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 Mg2+, but not Ca2+ 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 Mg2+. 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.