DIFFERENTIAL ROLES OF SELECTINS AND THE ALPHA(4)-INTEGRIN IN ACUTE, SUBACUTE, AND CHRONIC LEUKOCYTE RECRUITMENT IN-VIVO

Adhesion blocking mAbs specific for rat P-, E-, and L-selectin and the alpha(4)-integrin were used to characterize leukocyte recruitment mec hanisms in models of LTC, (acute), LPS (subacute), and adjuvant-induce d (chronic) inflammation, Intravital microscopy was employed to measur e leukocyte rolling and adhesion In rat mesenteric venules, Superfusin g the mesentery with 20 nM LTC4 elicited an increase in leukocyte roll ing (66.8 +/- 3.8 vs 18.2 +/- 3.2 cells/min control) that was complete ly eliminated by an anti-rat P-selectin mAb. Superfusion with 1 mu g/m l LPS induced a significant increase in leukocyte rolling within 15 mi n (73 +/- 8 vs 33 +/- 6 cells/min control). Rolling increased further starting at 105 min and peaked by 150 min (141 +/- 23 cells/min). LPS- induced leukocyte rolling was eliminated during the first 90 min by th e P-selectin mAb, The later increase in leukocyte rolling was not prev ented by a second treatment with P-selectin mAb or a function-blocking mAb against rat E-selectin. This later phase of leukocyte rolling was blocked by treatments with mAbs against either the alpha(4)-integrin or L-selectin. Twelve days following Mycobacterium butyricum immunizat ion, 300 to 500 rolling cells/min were observed, This could tee reduce d similar to 50 to 60% by mAb against either the alpha(4)-integrin or L-selectin. The combination of both mAbs eliminated similar to 90% of rolling, Neither the P- nor E-selectin mAbs reduced !oiling in this ch ronic inflammatory model, This study highlights differences in leukocy te adhesive mechanisms elicited by different stimuli and at different time points within the same vascular bed.