Isolated Pneumocystis carinii cell wall glucan provokes lower respiratory tract inflammatory responses

Robert Vassallo, Joseph E. Standing, Andrew H. Limper

Research output: Contribution to journalArticlepeer-review

123 Scopus citations

Abstract

Macrophage-induced lung inflammation contributes substantially to respiratory failure during Pneumocystis carinii pneumonia. We isolated a P. carinii cell wall fraction rich in glucan carbohydrate, which potently induces TNF-α and macrophage-inflammatory protein-2 generation from alveolar macrophages. Instillation of this purified P. carinii carbohydrate cell wall fraction into healthy rodents is accompanied by substantial increases in whole lung TNF-α generation and is associated with neutrophilic infiltration of the lungs. Digestion of the P. carinii cell wall isolate with zymolyase, a preparation containing predominantly β-1,3 glucanase, substantially reduces the ability of this P. carinii cell wall fraction to activate alveolar macrophages, thus suggesting that β-glucan components of the P. carinii cell wall largely mediate TNF-α release. Furthermore, the soluble carbohydrate β-glucan receptor antagonists laminariheptaose and laminarin also substantially reduce the ability of the P. carinii cell wall isolate to stimulate macrophage-inflammatory activation. In contrast, soluble α-mannan, a preparation that antagonizes macrophage mannose receptors, had minimal effect on TNF-α release induced by the P. carinii cell wall fraction. P. carinii β-glucan-induced TNF-α release from alveolar macrophages was also inhibited by both dexamethasone and pentoxifylline, two pharmacological agents with potential activity in controlling P. carinii-induced lung inflammation. These data demonstrate that P. carinii β-glucan cell wall components can directly stimulate alveolar macrophages to release proinflammatory cytokines mainly through interaction with cognate β-glucan receptors on the phagocyte.

Original languageEnglish (US)
Pages (from-to)3755-3763
Number of pages9
JournalJournal of Immunology
Volume164
Issue number7
DOIs
StatePublished - Apr 1 2000

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Isolated Pneumocystis carinii cell wall glucan provokes lower respiratory tract inflammatory responses'. Together they form a unique fingerprint.

Cite this