title: CD31-triggered rearrangement of the actin cytoskeleton in human natural killer cells.
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 alpha v and alpha L, whose function is known to depend on Mg2+. However, the CD31-induced cytoskeletal rearrangement was not reduced by the use of alpha v- or alpha L-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 cAMPS 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.
authors.affiliation: Laboratory of Immunopathology, National Institute for Cancer Research-ABC, Genoa, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Poggi
authors.forename: M C
authors.initials: MC
authors.lastname: Panzeri
authors.forename: L
authors.initials: L
authors.lastname: Moretta
authors.forename: M R
authors.initials: MR
authors.lastname: Zocchi
mesh_terms: D016475:3T3 Cells; D000199:Actins / Q000378:metabolism*; D000818:Animals; D015214:Antigens, Differentiation, Myelomonocytic / Q000502:physiology*; D002118:Calcium / Q000494:pharmacology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology*; D048429:Cell Size; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism* / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D016023:Integrins / Q000502:physiology; D007694:Killer Cells, Natural / Q000502:physiology* / Q000648:ultrastructure; D008274:Magnesium / Q000494:pharmacology; D051379:Mice; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015290:Second Messenger Systems / Q000502:physiology*; D013873:Thionucleotides / Q000494:pharmacology; D014162:Transfection
chemical_list: D000199:Actins; D015214:Antigens, Differentiation, Myelomonocytic; D015815:Cell Adhesion Molecules; D016023:Integrins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011993:Recombinant Fusion Proteins; D013873:Thionucleotides; D005576:Colforsin; C016957:adenosine-3',5'-cyclic phosphorothioate; D000242:Cyclic AMP; D008274:Magnesium; D002118:Calcium