Lymphocyte adhesion can be regulated by cytoskeleton-associated, PMA-induced capping of surface receptors.
Intercellular adhesion in lymphocytes is mediated in part by the interaction of the integrin lymphocyte function-associated antigen-1 (LFA-1) with intercellular adhesion molecule-1 (ICAM-1). The B lymphoblastoid line JY expresses both LFA-1 and ICAM-1, and intercellular adhesion is enhanced by treatment with the phorbol ester phorbol 12-myristate 13-acetate (PMA), which also induced capping of LFA-1, ICAM-1, and human leukocyte antigen. Capping of LFA-1 is likely to result from protein kinase C (PKC) activation because receptor-mediated stimulation of PKC also led to capping. Additionally, adhesion mediated by PMA or lipopolysaccharide was blocked by either of two PKC inhibitors, calphostin C and staurosporine. PMA induced the apparent condensation of cytoskeletal elements that colocalized with the membrane protein cap. Cytoskeletal condensation and capping occurred in the absence of intercellular adhesion. Alteration in the distribution of cytoskeletal components and membrane redistribution of LFA-1 were inhibited by cytochalasin D, which also abolished intercellular adhesion. Taken together, these data suggest that intercellular adhesion is the result of PKC-mediated membrane redistribution of LFA-1 and ICAM-1, which is in turn associated with modification of the actin-based cytoskeleton.
Haverstick
D M
DM
Department of Pathology, University of Virginia Health Sciences Center, Charlottesville 22908.
Sakai
H
H
Gray
L S
LS
D000199:Actins / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000648:ultrastructure; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000276:immunology* / Q000648:ultrastructure; D004789:Enzyme Activation; D006801:Humans; D007152:Immunologic Capping; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000378:metabolism; D008214:Lymphocytes / Q000502:physiology*; D008854:Microscopy, Electron; D011493:Protein Kinase C / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000199:Actins; D000954:Antigens, Surface; D016169:Lymphocyte Function-Associated Antigen-1; D011971:Receptors, Immunologic; D015638:Cytochalasin D; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate