Published online before print August 17, 2004
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Physiology Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts
@ To whom correspondence should be addressed. 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 macrophages (AMs) and peritoneal exudate macrophages (PEMs). Immobilized anti-SR-A (2F8) and anti-Fc receptor for immunoglobulin G (Fc
R)II/III (2.4G2) mAb stimulated hydrogen peroxide (H2O2) production in normal C3H/HeJ AMs (by 55% and 98%, respectively) and resident PEMs (66% and 128%). The 2F8 mAb-stimulated H2O2 production resulted from specific stimulation of SR-A, as 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-FcRII/III mAb was preserved in FcRI/III-deficient mice, ruling out involvement of FcRs in the 2F8 mAb effect. In comparison with the FcR-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--stimulated interleukin-12 (IL-12) release, by 25% in AMs and by 68% in thioglycollate-elicited PEMs, 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, as 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 receptors • knockout • alveolar • peritoneal • hydrogen peroxide
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