Engagement of ICAM-1 by major group rhinoviruses activates the LFA-1/ICAM-3 cell adhesion pathway in mononuclear phagocytes.
Cell-cell interactions are critical at key points of immune responses and are mediated by a complex array of adhesion receptors. One of the most important adhesion molecules on leukocytes is intercellular adhesion molecule 1 (ICAM-1, CD54). Here we demonstrate that engagement of ICAM-1 with human major group rhinoviruses (HRV) enhances adhesiveness and homotypic aggregation of human monocytes and monocyte-derived dendritic cells (DC). Cluster formation upon engagement of ICAM-1 with HRV14 represents an active process. It is temperature and energy dependent, requires divalent cations, an intact cytoskeleton and protein de novo synthesis. Homotypic interaction between monocytes induced by HRV14 can be inhibited with blocking mAbs against LFA-1 (CD11a/CD18) and ICAM-3 (CD50) as well as with a mAb against the first immunoglobulin (Ig)-domain of PECAM-1 (CD31). Induction of enhanced cytoadhesiveness by HRV14 was not accompanied with an upregulation of LFA-1, ICAM-3 or PECAM-1 expression. Binding studies with recombinant PECAM-1 proteins indicated, however, that monocyte clustering upon engagement of ICAM-1 with HRV was accompanied with increased homophilic PECAM-1 interactions. Taken together the results of our study demonstrate that signalling via ICAM-1 induces adhesiveness of mononuclear phagocytes, which critically involves PECAM-1 and is mediated via LFA-1/ICAM-3.
Kirchberger
Stefanie
S
Institute of Immunology, Medical University of Vienna, Borschkegasse 8a, A-1090, Austria.
Vetr
Helga
H
Majdic
Otto
O
Stockinger
Hannes
H
Stöckl
Johannes
J
D015703:Antigens, CD / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D012229:Rhinovirus / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; C483616:ICAM3 protein, human; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1