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

Andrew H. Limper, Jacques S. Hoyte, Joseph E. Standing

Research output: Contribution to journalArticlepeer-review

156 Scopus citations

Abstract

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 35S-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.

Original languageEnglish (US)
Pages (from-to)2110-2117
Number of pages8
JournalJournal of Clinical Investigation
Volume99
Issue number9
DOIs
StatePublished - May 1 1997

Keywords

  • Pneumocystis carinii
  • bisphosphonates
  • liposome
  • macrophage
  • phagocytosis

ASJC Scopus subject areas

  • Medicine(all)

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