Signaling through CD50 (ICAM-3) stimulates T lymphocyte binding to human umbilical vein endothelial cells and extracellular matrix proteins via an increase in beta 1 and beta 2 integrin function.
Regulated adhesion of T lymphocytes to antigen-presenting cells, endothelial cells and extracellular matrix proteins is crucial in T lymphocyte activation and migration to the sites of injury. In this study, we show that three monoclonal antibodies (mAb) recognizing different epitopes on the CD50 (ICAM-3) molecule increase T lymphocyte adhesion to tumor necrosis factor (TNF)-stimulated human umbilical vein endothelial cells and extracellular matrix proteins. These phenomena are mediated by an increase in beta 1 and beta 2 integrin avidity since (a) CD50-induced adhesion to endothelial cells was abrogated by simultaneous blocking of beta 1- and beta 2-mediated adhesion pathways but not by interfering with either one individually, (b) CD50 mAb increased beta 1 integrin-mediated adhesion to extracellular matrix proteins and to fibronectin-derived synthetic peptides, (c) CD50 mAb enhanced T lymphocyte binding to ICAM-1 transfectants, and (d) CD50 mAb did not modify surface expression patterns of beta 1 or beta 2 integrins on T lymphocytes. Our data suggest that constitutively expressed CD50 (ICAM-3) can play a pivotal role in initiating a cascade of adhesion events which may be crucial in immune activation and in the development of inflammatory lesions.
Cid
M C
MC
Department of Immunology, Hospital Clinic i Provincial, Barcelona, Spain.
Esparza
J
J
Juan
M
M
Miralles
A
A
Ordi
J
J
Vilella
R
R
Urbano-Márquez
A
A
Gayà
A
A
Vives
J
J
Yagüe
J
J
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018821:CD18 Antigens; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002449:Cell Aggregation / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology*; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D019012:Integrin beta1; D016023:Integrins / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1; D013601:T-Lymphocytes / Q000502:physiology*; D014471:Umbilical Veins / Q000166:cytology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D005353:Fibronectins; C483616:ICAM3 protein, human; D019012:Integrin beta1; D016023:Integrins; D018799:Intercellular Adhesion Molecule-1