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 beta(2)-integrin activity.