VASCULAR BIOLOGY

Patients with antineutrophil cytoplasmic an-tibodies (ANCAs) frequently develop severe vasculitis and glomerulonephritis. Although ANCAs, particularly antimyeloperoxidase (anti-MPO), have been shown to promote leukocyte adhesion in postcapillary venules, their ability to promote adhesion in the glo-merular vasculature is less clear. We used intravital microscopy to examine glomerular leukocyte adhesion induced by anti-MPO. In mice pretreated with LPS, 50 g anti-MPO induced LFA-1–dependent adhesion in glo-meruli. In concert with this finding, in mice pretreated with LPS, more than 80 % of circu-lating neutrophils bound anti-MPO within 5 minutes of intravenous administration. However, even in the absence of LPS, more than 40 % of circulating neutrophils bound anti-MPO in vivo, a response not seen in MPO/ mice. In addition, a higher dose of anti-MPO (200 g) induced ro-bust glomerular leukocyte adhesion in the absence of LPS. The latter response was2-integrin independent, instead requir-ing the 4-integrin, which was up-regulated on neutrophils in response to anti-MPO. These data indicate that anti-MPO antibod-ies bind to circulating neutrophils, and can induce glomerular leukocyte adhesion via multiple pathways. Lower doses induce ad-hesion only after an infection-related stimu-lus, whereas higher doses are capable of inducing responses in the absence of an additional inflammatory stimulus, via alter-native adhesion mechanisms. (Blood. 2009; 113:6485-6494