Journal of Leukocyte Biology Myeloid cells, immune suppression, tumor immunology
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Originally published online as doi:10.1189/jlb.0504270 on August 17, 2004

Published online before print August 17, 2004
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(Journal of Leukocyte Biology. 2004;76:1066-1074.)
© 2004 by Society for Leukocyte Biology

Scavenger receptor A mediates H2O2 production and suppression of IL-12 release in murine macrophages

Szczepan Józefowski1 and Lester Kobzik

Physiology Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts

1 Correspondence: Harvard School of Public Health, 665 Huntington Avenue, SPH-2, Room 223, Boston, MA 02115. E-mail: sjozefow{at}hsph.harvard.edu

Although class A type I/II scavenger receptor (SR-A) is involved in numerous macrophage functions, its signaling ability remains uncertain. We used monoclonal antibodies (mAb) to specifically stimulate receptors on mouse alveolar (AMs) and peritoneal macrophages (PMs). Immobilized anti-SR-A (2F8) and anti-Fc{gamma}R II/III (2.4G2) mAb stimulated hydrogen peroxide (H2O2) production in normal C3H/HeJ AMs (by 55% and 98%, respectively) and resident PMs (66% and 128%). The 2F8 mAb-stimulated H2O2 production resulted from specific stimulation of SR-A, since this response was absent in AMs from SR-A-deficient or C57BL/6 mice—the latter strain expressing an allelic form of SR-A, unrecognizable by 2F8 mAb. H2O2 production stimulated by anti-SR-A but not by anti-Fc{gamma}RII/III mAb was preserved in Fc{gamma}RI/III-deficient mice, ruling out involvement of Fc{gamma}Rs in the 2F8 mAb effect. In comparison with the Fc{gamma}R-stimulated respiratory burst, the response to anti-SR-A mAb was delayed and, unlike the former, inhibited by pertussis toxin. Ligation of SR-A also inhibited lipopolysaccharide plus interferon-{gamma}-stimulated interleukin-12 (IL-12) release, by 25% in AMs and by 68% in thioglycollate-elicited PMs, consistent with different levels of SR-A expression. Neither nitrite nor IL-6 accumulation was affected by anti-SR-A mAb. SR-A-stimulated H2O2 does not seem to mediate the inhibition of IL-12 release, since the inhibition was neither reversed by scavenging of H2O2 nor mimicked by exogenous H2O2. Our results indicate that SR-A not only mediates endocytosis but can also generate signals such as H2O2, which may affect microbicidal or proinflammatory functions.

Key Words: Fc{gamma} receptors • knockout • alveolar • peritoneal • hydrogen peroxide




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