Am. J. Respir. Cell Mol. Biol., Volume 23, Number 4, October, 2000 452-459

Alveolar Macrophages from Human Immunodeficiency Virus-Infected Persons Demonstrate Impaired Oxidative Burst Response to Pneumocystis carinii In Vitro

Henry Koziel, Xiuhong Li, Martine Y. K. Armstrong, Frank F. Richards, and Richard M. Rose^*

Division of Pulmonary and Critical Care Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts; and MacArthur Center for Molecular Parasitology, Yale University School of Medicine, New Haven, Connecticut

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 [H₂O₂] 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 µg/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 H₂O₂ production was significantly reduced in AMs from asymptomatic HIV-positive (HIV+) persons with CD4+ counts < 200 cells/mm³ (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/mm³. 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.

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