T cell adhesion to endothelial cells and extracellular matrix is modulated upon transendothelial cell migration.
During inflammation, T cells transmigrate from the bloodstream into perivascular tissues. As T cells transmigrate, they undergo a series of attachments to and detachments from the endothelium and then extravasate into the extracellular matrix (ECM). T cell migration into the ECM involves a number of mechanisms that influence cell-ECM interactions. The modulation of integrin expression and affinity are two such mechanisms in which cells can alter their ability to interact with other cells and ECM. We show in vitro that transmigrated T cells exhibit down-regulation of very late activation antigen-4 and leukocyte function-associated antigen-1 integrin surface expression and a decrease in binding to recombinant vascular cell adhesion molecule-1 and recombinant intercellular adhesion molecule-1. Also, transmigrated T cells displayed an increase in binding to collagens I and IV and fibronectin. Further, brain sections of experimental autoimmune encephalomyelitis mice demonstrated that as T cells migrated farther into the tissue, very late activation antigen-4 expression was lost while CD4 expression remained unchanged. The significance of these findings in the modulation of the inflammatory response is discussed.
Romanic
A M
AM
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Graesser
D
D
Baron
J L
JL
Visintin
I
I
Janeway
C A
CA
Madri
J A
JA
D000818:Animals; D001921:Brain / Q000276:immunology / Q000473:pathology; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D003094:Collagen / Q000502:physiology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology; D004730:Endothelium, Vascular / Q000276:immunology / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology*; D005353:Fibronectins / Q000502:physiology; D005434:Flow Cytometry; D039041:Integrin alpha4beta1; D016023:Integrins / Q000096:biosynthesis; D018799:Intercellular Adhesion Molecule-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis; D051379:Mice; D008815:Mice, Inbred Strains; D004676:Myelin Basic Protein / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis; D016029:Receptors, Very Late Antigen / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000494:pharmacology / Q000502:physiology
D005353:Fibronectins; D039041:Integrin alpha4beta1; D016023:Integrins; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D016201:Receptors, Lymphocyte Homing; D016029:Receptors, Very Late Antigen; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D003094:Collagen