Alveolar macrophages from human immunodeficiency virus-infected persons demonstrate impaired oxidative burst response to Pneumocystis carinii in vitro.
The alveolar macrophage (AM) oxidative burst response is an important component of microbicidal effector cell function against a variety of potential pathogens in the lungs, although the role against Pneumocystis carinii has not been fully investigated. The goals of this study were to characterize the P. carinii-mediated oxidative burst of AMs from healthy individuals, and to examine the oxidative burst of AMs from human immunodeficiency virus (HIV)-infected persons. For healthy individuals, the AM oxidative burst (measured as hydrogen peroxide [H(2)O(2)] production) increased in a time- and concentration-dependent manner in response to P. carinii or to the major surface glycoprotein of P. carinii, gp-A (0.01 to 10 microg/ml), required physical contact of P. carinii with AMs, and was not dependent on organism viability. Enzymatic removal of the surface-associated molecules of P. carinii reduced the oxidative burst to 43% of control (P = 0.01). Blocking the AM mannose receptor reduced the P. carinii-mediated oxidative burst response to 37% of control (P = 0.01). Compared with AMs from healthy individuals, P. carinii-mediated H(2)O(2) production was significantly reduced in AMs from asymptomatic HIV-positive (HIV+) persons with CD4+ counts < 200 cells/mm(3) (249+/-43 relative fluorescence units [RFU] versus 130+/-44 RFU; mean +/- standard error of the mean, P = 0.038) and HIV+ persons with active P. carinii pneumonia (78+/-40 RFU; P = 0.014), but preserved for HIV+ persons with CD4+ counts > 200 cells/mm(3). Importantly, H2O2 production in response to phorbol myristate acetate or serum-opsonized zymosan particles was preserved in all groups studied. Thus, AM oxidative burst, mediated in part via P. carinii gp-A and AM mannose receptor may represent an important host response to P. carinii. A specific impairment of P. carinii-mediated AM oxidative burst in persons with advanced HIV infection may contribute to the pathogenesis of P. carinii pneumonia.
Koziel
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Division of Pulmonary and Critical Care Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA. hkoziel@caregroup.harvard.edu
Li
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Armstrong
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Richards
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Rose
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D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D016022:Case-Control Studies; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D018023:HIV Seronegativity / Q000276:immunology; D006801:Humans; D016676:Macrophages, Alveolar / Q000276:immunology*; D008297:Male; D011010:Pneumocystis / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D016897:Respiratory Burst
D017382:Reactive Oxygen Species