TY - JOUR
T1 - Antimyeloperoxidase antibodies rapidly induce alpha4-integrin-dependent glomerular neutrophil adhesion
AU - Kuligowski, Michael Peter
AU - Kwan, Rain
AU - Lo, Cecilia
AU - Wong, Cyndi
AU - James, William Geraint Moulton
AU - Bourges, Dorothee
AU - Ooi, Joshua D
AU - Abeynaike, Latasha
AU - Hall, Pamela Heidi
AU - Kitching, Arthur Richard
AU - Hickey, Michael John
PY - 2009
Y1 - 2009
N2 - Antimyeloperoxidase antibodies rapidly induce alpha-4-integrin-dependent glomerular neutrophil adhesion. Patients with antineutrophil cytoplasmic antibodies (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 glomerular vasculature is less clear. We used intravital microscopy to examine glomerular leukocyte adhesion induced by anti-MPO. In mice pretreated with LPS, 50 microg anti-MPO induced LFA-1-dependent adhesion in glomeruli. In concert with this finding, in mice pretreated with LPS, more than 80 of circulating 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 microg) induced robust glomerular leukocyte adhesion in the absence of LPS. The latter response was beta2-integrin independent, instead requiring the alpha4-integrin, which was up-regulated on neutrophils in response to anti-MPO.
AB - Antimyeloperoxidase antibodies rapidly induce alpha-4-integrin-dependent glomerular neutrophil adhesion. Patients with antineutrophil cytoplasmic antibodies (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 glomerular vasculature is less clear. We used intravital microscopy to examine glomerular leukocyte adhesion induced by anti-MPO. In mice pretreated with LPS, 50 microg anti-MPO induced LFA-1-dependent adhesion in glomeruli. In concert with this finding, in mice pretreated with LPS, more than 80 of circulating 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 microg) induced robust glomerular leukocyte adhesion in the absence of LPS. The latter response was beta2-integrin independent, instead requiring the alpha4-integrin, which was up-regulated on neutrophils in response to anti-MPO.
UR - http://www.scopus.com/record/display.url?eid=2-s2.0-67650578429&origin=inward&txGid=paNYetlG12vbuVnW8584QfF%3a10
U2 - 10.1182/blood-2008-12-192617
DO - 10.1182/blood-2008-12-192617
M3 - Article
SN - 0006-4971
VL - 113
SP - 6485
EP - 6494
JO - Blood
JF - Blood
IS - 25
ER -