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(Journal of Leukocyte Biology. 2000;68:679-686.)
© 2000 by Society for Leukocyte Biology

C5a-stimulated human neutrophils use a subset of ß₂ integrins to support the adhesion-dependent phase of superoxide production

ShivRaj Tyagi^*,, Lloyd B. Klickstein^, and Anne Nicholson-Weller^*,

^* Divisions of Infectious Diseases and Allergy and Inflammation, Department of Medicine, and Charles A. Dana Research Institute and Harvard-Thorndike Laboratory, Beth Israel Deaconess Medical Center; and
Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital,
Harvard Medical School, Boston, Massachusetts

Correspondence: Dr. Anne Nicholson-Weller, M.D., Dana 617, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215. E-mail: anichols{at}caregroup.harvard.edu

Isolated human polymorphonuclear neutrophils (PMN) responded to human C5a with an immediate, transient release of superoxide lasting from 0.5 to 5 min. This was followed by a second release of superoxide, which began at 10 min after addition of C5a, was sustained for more than 30 min, and required ICAM-1 immobilized in the wells. F(ab')₂ monoclonal antibody (mAb) preparations were used to dissect the role of individual ß₂ integrins and to avoid the confounding effects of ligating Fc receptors. Anti-CD18 mAb treatment of the PMN had no effect on the immediate first phase but completely inhibited the second, adhesion-dependent phase of superoxide production. Anti-CR3 mAb only inhibited the adhesion phase of superoxide production partially, implying that other ß₂ integrins were involved. A mixture of anti-CD11a, anti-CD11b, and anti-CD11c was not able to block superoxide production completely, suggesting a role for d/ß₂. Surprisingly, blocking anti-LFA-1 mAb had no effect on superoxide production. Consistent with this observation, immobilized, purified ICAM-2, a specific counter-receptor for LFA-1, did not support the adhesion-dependent phase ofsuperoxide production. Thus, PMN treated with C5a used signals via CR3, P150/95, and d/ß₂, but not LFA-1, to support superoxide production. LFA-1 has been shown by others to mediate most of the adhesion necessary for transendothelial migration in vivo. The inability of LFA-1 ligation to stimulate superoxide production may be an important means of preventing blood-vessel damage when PMN migrate across the endothelium.

Key Words: human • complement • free radicals • inflammatory mediators

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