EFFECTS OF DIFFERENT MEDIATORS OR CYTOKINES AND MONOCLONAL-ANTIBODIESTO ADHESION MOLECULES ON LEUKOCYTE ADHESION IN RAT MESENTERIC VENULES

Leukocyte adhesion (LA) to the endothelium of postcapillary venules is considered to be an important step in the inflammatory response. The recruitment of blood leukocytes into sites of inflammation involves a well-coordinated and dynamic sequence of events in which several cellu lar adhesion molecules (CAMs) and chemotactic cytokines play an active role. The aim of the present study was to elucidate receptor-mediated interaction in mesenteric venules of leukocyte rolling/adhesion and p lasma leakage. We applied intravital microscopic techniques, with the help of an analogous video image processing system, to measure changes in the microvascular integrity. Rat monoclonal antibodies (MoAb) to d ifferent CAMs were administered before inflammatory stimuli were appli ed. Topical application of different doses of either lipopolysaccharid e (LPS), fMet-Leu-Phe, zymosan, complement C5a, TNF-alpha, interleukin -1 beta (IL-1 beta), IL2 or IL-6 resulted in a dose-dependent increase in LA. The injection of a MoAb (1 mg/kg), 15 min prior to the LPS cha llenge, resulted in (1) total inhibition of LA, when MoAb to rat L-sel ectin, LFA1-beta and VLA-4 were used, (2) a moderate effect with LFA-1 beta and Mac-1 MoAb, and (3) only a weak influence on LA by the MoAb to rat ICAM-1 (1 mg/kg). No effects were seen with IgG1 control MoAb. LA in acute models of inflammation can be regarded as a consequence of time-dependent differential effects of CAMs, as observed through the application of different MoAb.