Koziel H, Li X, Armstrong M Y, Richards F F, Rose R M
Division of Pulmonary and Critical Care Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
Am J Respir Cell Mol Biol. 2000 Oct;23(4):452-9. doi: 10.1165/ajrcmb.23.4.4084.
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.
肺泡巨噬细胞（AM）的氧化爆发反应是肺部针对多种潜在病原体的杀菌效应细胞功能的重要组成部分，尽管其在对抗卡氏肺孢子虫方面的作用尚未得到充分研究。本研究的目的是表征健康个体的AM对卡氏肺孢子虫介导的氧化爆发，并检查人类免疫缺陷病毒（HIV）感染者的AM的氧化爆发。对于健康个体，AM的氧化爆发（以过氧化氢[H₂O₂]产生量衡量）在响应卡氏肺孢子虫或卡氏肺孢子虫的主要表面糖蛋白gp-A（0.01至10微克/毫升）时，呈时间和浓度依赖性增加，需要卡氏肺孢子虫与AM进行物理接触，且不依赖于生物体的活力。酶促去除卡氏肺孢子虫的表面相关分子可使氧化爆发降低至对照的43%（P = 0.01）。阻断AM甘露糖受体可使卡氏肺孢子虫介导的氧化爆发反应降低至对照的37%（P = 0.01）。与健康个体的AM相比，CD4⁺细胞计数<200个细胞/立方毫米的无症状HIV阳性（HIV⁺）者的AM中，卡氏肺孢子虫介导的H₂O₂产生量显著降低（249±43相对荧光单位[RFU]对130±44 RFU；平均值±平均标准误差，P = 0.038），患有活动性卡氏肺孢子虫肺炎的HIV⁺者的AM中也是如此（78±40 RFU；P = 0.014），但CD4⁺细胞计数>200个细胞/立方毫米的HIV⁺者的AM中该产生量得以保留。重要的是，在所有研究组中，对佛波酯肉豆蔻酸酯或血清调理的酵母聚糖颗粒的H₂O₂产生量均得以保留。因此，部分通过卡氏肺孢子虫gp-A和AM甘露糖受体介导的AM氧化爆发可能代表了宿主对卡氏肺孢子虫的重要反应。晚期HIV感染者中卡氏肺孢子虫介导的AM氧化爆发的特异性损害可能有助于卡氏肺孢子虫肺炎的发病机制。
