Document Detail

Leukocyte function-associated antigen 1 (LFA-1) and CD44 are signalling molecules for cytoskeleton-dependent morphological changes in activated T cells.
MedLine Citation:
PMID:  7595055     Owner:  NLM     Status:  MEDLINE    
Signaling through the leukocyte function-associated antigen 1 (LFA-1) molecule has previously been shown to induce homotypic aggregation in T cells and to induce cytoskeletal changes in T lymphoma cells. In this study we describe the induction of a dendritic phenotype associated with cytoskeletal rearrangement in activated human peripheral blood T cells stimulated with monoclonal antibody SPV-L7 to LFA-1 alpha. Maximal expression of this phenotype required 72 h preactivation with phorbol myristate acetate and expression was abolished using the protein kinase C inhibitor staurosporine. Monoclonal antibody to CD18, the beta-chain of LFA-1, did not induce this phenotype. Monoclonal antibody MEM 83 to presumably a discrete epitope on LFA-1 alpha did not induce this phenotype but induced homotypic aggregation. However, a monoclonal antibody to CD44 induced a similar phenotype in activated lymphocytes. Induction of both homotypic in activated lymphocytes. Induction of both homotypic aggregation and the dendritic phenotype was abolished by preincubation with soluble intracellular adhesion molecule 1 (ICAM-1). Cytoskeletal inhibitors prevented the morphological changes in SPV-L7-activated lymphocytes. Preincubation with tyrosine kinase inhibitor, protein kinase C inhibitors, and inhibitors of new protein synthesis also prevented these morphological changes. These data suggest that discrete epitopes on LFA-1 alpha may be capable of inducing discrete signals either for homotypic aggregation or for a dendritic phenotype. As both LFA-1 and CD44 are involved in the migration of lymphocytes through high endothelial venules, these data could suggest that these molecules transduce signals resulting in cytoskeletal modification necessary for lymphocyte transmigration.
D Kelleher; A Murphy; C Feighery; E B Casey
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of leukocyte biology     Volume:  58     ISSN:  0741-5400     ISO Abbreviation:  J. Leukoc. Biol.     Publication Date:  1995 Nov 
Date Detail:
Created Date:  1995-12-19     Completed Date:  1995-12-19     Revised Date:  2009-09-29    
Medline Journal Info:
Nlm Unique ID:  8405628     Medline TA:  J Leukoc Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  539-46     Citation Subset:  IM    
Department of Clinical Medicine, Trinity College Dublin, Ireland.
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MeSH Terms
Alkaloids / pharmacology
Antigens, CD2 / metabolism
Antigens, CD3 / physiology
Antigens, CD44 / physiology*
Cell Membrane / ultrastructure
Cell Size / drug effects
Cytoskeleton / physiology*,  ultrastructure
Enzyme Inhibitors / pharmacology
Intercellular Adhesion Molecule-1 / pharmacology
Lymphocyte Activation*
Lymphocyte Function-Associated Antigen-1 / physiology*
Protein Kinase C / antagonists & inhibitors,  physiology
Signal Transduction
T-Lymphocytes / cytology*
Tetradecanoylphorbol Acetate / pharmacology
Grant Support
//Wellcome Trust
Reg. No./Substance:
0/Alkaloids; 0/Antigens, CD2; 0/Antigens, CD3; 0/Antigens, CD44; 0/Enzyme Inhibitors; 0/Lymphocyte Function-Associated Antigen-1; 126547-89-5/Intercellular Adhesion Molecule-1; 16561-29-8/Tetradecanoylphorbol Acetate; 62996-74-1/Staurosporine; EC Kinase C

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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