Participation of CD11a-c/CD18 and RGD-recognizing adhesion molecules in the binding of LGL to fibroblasts. Evidence for the role of CD11a in the fibroblast-mediated inactivation of NK cells.
We have previously shown that large granular lymphocytes (LGL) are inactivated by contact with natural killer (NK) resistant monolayer target cells. In this work we have analysed which adhesion molecules are involved in the binding of LGL to such targets, as exemplified by fibroblasts, and in the subsequent inhibition of their NK activity. The results indicate that antibodies against CD54 (intercellular adhesion molecule 1, ICAM-1), CD11a (leucocyte function antigen 1, LFA-1, alpha chain), and CD18 (common beta chain of the beta 2-integrin family) significantly (by 50%) reduce the binding of LGL onto inhibitory target cells. The matrix protein-based synthetic peptide RGD and anti-CD29 (the common beta chain of the beta 2-integrin family) antibodies also diminish the binding (by 35%). The effects of the antiadhesion molecule antibodies and the peptide are additive, the combination of both leading to an almost complete block of adhesion. It may be hypothesized that some of the binding-relevant adhesion molecules of the RGD-binding domain on LGL (CD29) may be involved in the delivery of the inactivating signal to the effector cell. Indeed, incubation of LGL with anti-CD11a antibodies, but neither with antibodies against other binding-relevant epitopes nor with RGD, significantly reduced their NK activity. The mechanism of the inactivation was similar to that induced by intact NK-resistant target cells. On the basis of the present results we suggest that the CD11a molecule is involved in the down-regulation of the NK activity of peripheral blood lymphocytes.
Department of Pathology, University of Helsinki, Finland.
M K
MK
Heiskala
M
M
Patarroyo
T T
TT
Timonen
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation / Q000276:immunology*; D018845:CD11 Antigens; D018821:CD18 Antigens; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D005347:Fibroblasts / Q000276:immunology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007694:Killer Cells, Natural / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D009842:Oligopeptides / Q000276:immunology; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D018845:CD11 Antigens; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D000939:Epitopes; D009842:Oligopeptides; D016028:Receptors, Leukocyte-Adhesion; D018799:Intercellular Adhesion Molecule-1; C046617:arginyl-glycyl-aspartyl-serine