Antimyeloperoxidase antibodies rapidly induce alpha4-integrin-dependent glomerular neutrophil adhesion

Michael Peter Kuligowski, Rain Kwan, Cecilia Lo, Cyndi Wong, William Geraint Moulton James, Dorothee Bourges, Joshua D Ooi, Latasha Abeynaike, Pamela Heidi Hall, Arthur Richard Kitching, Michael John Hickey

Research output: Contribution to journal › Article › Research › peer-review

Abstract

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.
Original languageEnglish
Pages (from-to)6485 - 6494
Number of pages10
JournalBlood
Volume113
Issue number25
DOIs
Publication statusPublished - 2009

Cite this

Kuligowski, Michael Peter ; Kwan, Rain ; Lo, Cecilia ; Wong, Cyndi ; James, William Geraint Moulton ; Bourges, Dorothee ; Ooi, Joshua D ; Abeynaike, Latasha ; Hall, Pamela Heidi ; Kitching, Arthur Richard ; Hickey, Michael John. / Antimyeloperoxidase antibodies rapidly induce alpha4-integrin-dependent glomerular neutrophil adhesion. In: Blood. 2009 ; Vol. 113, No. 25. pp. 6485 - 6494.
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title = "Antimyeloperoxidase antibodies rapidly induce alpha4-integrin-dependent glomerular neutrophil adhesion",
abstract = "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.",
author = "Kuligowski, {Michael Peter} and Rain Kwan and Cecilia Lo and Cyndi Wong and James, {William Geraint Moulton} and Dorothee Bourges and Ooi, {Joshua D} and Latasha Abeynaike and Hall, {Pamela Heidi} and Kitching, {Arthur Richard} and Hickey, {Michael John}",
year = "2009",
doi = "10.1182/blood-2008-12-192617",
language = "English",
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pages = "6485 -- 6494",
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Kuligowski, MP, Kwan, R, Lo, C, Wong, C, James, WGM, Bourges, D, Ooi, JD, Abeynaike, L, Hall, PH, Kitching, AR & Hickey, MJ 2009, 'Antimyeloperoxidase antibodies rapidly induce alpha4-integrin-dependent glomerular neutrophil adhesion' Blood, vol. 113, no. 25, pp. 6485 - 6494. https://doi.org/10.1182/blood-2008-12-192617

Antimyeloperoxidase antibodies rapidly induce alpha4-integrin-dependent glomerular neutrophil adhesion. / Kuligowski, Michael Peter; Kwan, Rain; Lo, Cecilia; Wong, Cyndi; James, William Geraint Moulton; Bourges, Dorothee; Ooi, Joshua D; Abeynaike, Latasha; Hall, Pamela Heidi; Kitching, Arthur Richard; Hickey, Michael John.

In: Blood, Vol. 113, No. 25, 2009, p. 6485 - 6494.

Research output: Contribution to journal › Article › Research › peer-review

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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

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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.

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DO - 10.1182/blood-2008-12-192617

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SP - 6485

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JO - Blood

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SN - 0006-4971

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Kuligowski MP, Kwan R, Lo C, Wong C, James WGM, Bourges D et al. Antimyeloperoxidase antibodies rapidly induce alpha4-integrin-dependent glomerular neutrophil adhesion. Blood. 2009;113(25):6485 - 6494. https://doi.org/10.1182/blood-2008-12-192617

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