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Published online before print July 15, 2003

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(Journal of Leukocyte Biology. 2003;74:551-557.)
© 2003 by Society for Leukocyte Biology

Interaction of proteinase 3 with CD11b/CD18 (ß₂integrin) on the cell membrane of human neutrophils

A. David^*, Y. Kacher^*, U. Specks and I. Aviram^*,1

^* Department Biochemistry, Tel Aviv University, Israel; and
Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota

¹ Correspondence: Department of Biochemistry, Tel Aviv University, Tel Aviv 69978, Israel. E-mail: avirama{at}post.tau.ac.il

Proteinase 3 (PR3), the target autoantigen of antineutrophil cytoplasmic antibodies in the autoimmune vasculitis, Wegener’s granulomatosis, is a serine proteinase stored in granules of human neutrophils. As previously shown, PR3 is expressed also on the plasma membrane of unactivated neutrophils, and this expression increases in primed or stimulated cells. The current study demonstrates that membrane-bound PR3 colocalizes with the adhesion molecule CD11b/CD18 (ß₂ integrin). Immunoprecipitation experiments using plasma membranes of phorbol 12-myristate 13-acetate (PMA)-stimulated neutrophils revealed coimmunoprecipitation of PR3 with CD11b/CD18, indicating their location in the same complex. PR3 was also detected in TritonX-100-insoluble cytoskeleton of plasma membranes isolated from unactivated and activated neutrophils. Release of cytoskeletal PR3 by salt treatment implied electrostatic interaction with the enzyme. The serine protease inhibitor phenylmethylsulfonyl fluoride (PMSF) augmented membrane expression of PR3 in unactivated and PMA-stimulated neutrophils. PMSF significantly reduced adhesion of neutrophils to fibrinogen-coated plates and their NADPH oxidase activity. Moreover, the addition of exogenous PR3 (1–5 µg/ml) augmented the CD11b/CD18-dependent adhesion of neutrophils. Taken together, these results implicate the ß₂ integrin of neutrophils in their membrane association with PR3 and suggest a role of PR3 in the modulation of cell adhesion.

Key Words: adhesion • NADPH oxidase • serine protease • PMSF • cytoskeleton

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