PT  - JOURNAL ARTICLE
AU  - Vassallo, Robert
AU  - Standing, Joseph E.
AU  - Limper, Andrew H.
TI  - Isolated <em>Pneumocystis carinii</em> Cell Wall Glucan Provokes Lower Respiratory Tract Inflammatory Responses
AID  - 10.4049/jimmunol.164.7.3755
DP  - 2000 Apr 01
TA  - The Journal of Immunology
PG  - 3755--3763
VI  - 164
IP  - 7
4099  - http://www.jimmunol.org/content/164/7/3755.short
4100  - http://www.jimmunol.org/content/164/7/3755.full
SO  - J. Immunol.2000 Apr 01; 164
AB  - 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.