Inhibition and stimulation of LFA-1 and Mac-1 functions by antibodies against murine CD18. Evidence that the LFA-1 binding sites for ICAM-1, -2, and -3 are distinct.
The murine CD18 monoclonal antibody (mAb) M18/2 was reported to inhibit lymphoma metastasis [Zahalka, M. A. et al. (1993) J. Immunol. 150, 4466]. To identify the pathways potentially blocked, we studied the effects of M18/2 compared with two new mAb against murine CD18, GAME-46, and -245. Whereas the GAME mAb blocked most Mac-1-mediated interactions, M18/2 had no effect, or even stimulated. The same was true for adhesion of LFA-1 to ICAM-1. To test effects on interactions with different ICAMs, we used L cells transfected with human ICAM-1, -2, and -3. As previously described, mouse LFA-1 does not bind to human ICAM-1 but we show here that mouse LFA-1 does bind to human ICAM-2 and -3. Again, the GAME mAb blocked completely, but M18/2 did not. These results indicate that the LFA-1 binding sites for ICAM-1 and ICAM-2 and -3, although in close vicinity, are distinct. Furthermore, effects of M18/2 on metastasis cannot be ascribed to blocking of any known beta2-integrin activity.
Driessens
M H
MH
Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam.
van Hulten
P
P
Zuurbier
A
A
La Rivière
G
G
Roos
E
E
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000937:Antigen-Antibody Reactions; D015703:Antigens, CD / Q000378:metabolism*; D000943:Antigens, Differentiation; D001665:Binding Sites; D001667:Binding, Competitive; D018821:CD18 Antigens / Q000378:metabolism*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003179:Complement C3b / Q000378:metabolism; D000939:Epitopes; D005340:Fibrinogen / Q000378:metabolism; D005780:Gelatin / Q000378:metabolism; D006801:Humans; D006825:Hybridomas; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D008223:Lymphoma / Q000473:pathology; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D051379:Mice; D009362:Neoplasm Metastasis; D011233:Precipitin Tests; D051381:Rats; D013045:Species Specificity
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D000939:Epitopes; C065289:ICAM2 protein, human; C483616:ICAM3 protein, human; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D018799:Intercellular Adhesion Molecule-1; D003179:Complement C3b; D005780:Gelatin; D005340:Fibrinogen