The role of alveolar macrophages in Pneumocystis carinii degradation and clearance from the lung

被引:149
作者
Limper, AH [1 ]
Hoyte, JS [1 ]
Standing, JE [1 ]
机构
[1] MAYO CLIN & MAYO FDN,DEPT BIOCHEM & MOL BIOL,ROCHESTER,MN 55905
关键词
Pneumocystis carinii; macrophage; liposome; phagocytosis; bisphosphonates;
D O I
10.1172/JCI119384
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Although studies indicate that alveolar macrophages participate in host defense against Pneumocystis carinii, their role in organism degradation and clearance from the lung has not yet been established, We, therefore, quantified the uptake and degradation of S-35-labeled P. carinii by cultured macrophages, demonstrating significant degradation of P. carinii over 6 h. We further evaluated the role of macrophages in elimination of P. carinii from the living host, Rats received either intratracheal PBS, liposomal PBS (L-PBS), or liposomal dichloromethylene diphosphonate (L-Cl2MDP), a preparation which leads to selective depletion of macrophages, Over 72 h, L-Cl2MDP-treated animals had loss of > 85% of their alveolar macrophages. In contrast, L-PBS-treated rats had cellular differentials identical to rats receiving PBS, Macrophage-depleted rats and controls were next inoculated with P. carinii and organism clearance was determined after 24 h. P. carinii elimination was evaluated with both cyst counts and an ELISA directed against glycoprotein A (gpA), the major antigen of P. carinii. Both assays indicated that macrophage-depleted rats had substantial impairment of P. carinii clearance compared to L-PBS- or PBS-treated rats, These data provide the first direct evidence that macrophages mediate elimination of P. carinii from the living host.
引用
收藏
页码:2110 / 2117
页数:8
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