TY - JOUR
T1 - Pneumocystis carinii
T2 - Inhibition of lung cell growth mediated by parasite attachment
AU - Limper, A. H.
AU - Martin, W. J.
PY - 1990/2
Y1 - 1990/2
N2 - Pneumocystis carinii pneumonia is a significant cause of mortality in immunocompromised patients. Current concepts suggest that attachment of P. carinii to alveolar epithelium is required for development of pneumonia. We examined the mechanism of P. carinii adherence to cultured A549 cells, a permanent cell line derived from human alveolar epithelium. P. carinii adherence was quantified by measuring attachment of 51Cr-labeled P. carinii to cultured A549 cells. After 8 h of incubation, 37.4±4.2% of P. carinii were adherent to A549 cells. In the presence of agents known to impair cytoskeletal function, including 10-5 M cytochalasin B, 10-5 M colchicine, and 10-5 M trimethylcolchicinic acid (TMCA), adherence was decreased from 57.4±4.2% to 9.3±3.4%, 12.5±3.6%, and 21.5±3.6%, respectively (P < 0.01, all comparisons). Secondly, we examined the effect of P. carinii on the function of A549 cells. P. carinii resulted in significant impairment of A549 cell growth, indicating P. carinii adversely affected the function of target lung cells. A P. carinii: A549 cell ratio of 50:1 resulted in 43.5±2.9% inhibition of A549 cell growth (P < 0.001). Additionally, TMCA, which significantly prevented attachment of P. carinii, reversed the impairment of A549 cell growth. These data demonstrate that P. carinii attachment to cultured lung cells can be quantified, is dependent on intact cytoskeletal function and is necessary for impairment of lung cell replication.
AB - Pneumocystis carinii pneumonia is a significant cause of mortality in immunocompromised patients. Current concepts suggest that attachment of P. carinii to alveolar epithelium is required for development of pneumonia. We examined the mechanism of P. carinii adherence to cultured A549 cells, a permanent cell line derived from human alveolar epithelium. P. carinii adherence was quantified by measuring attachment of 51Cr-labeled P. carinii to cultured A549 cells. After 8 h of incubation, 37.4±4.2% of P. carinii were adherent to A549 cells. In the presence of agents known to impair cytoskeletal function, including 10-5 M cytochalasin B, 10-5 M colchicine, and 10-5 M trimethylcolchicinic acid (TMCA), adherence was decreased from 57.4±4.2% to 9.3±3.4%, 12.5±3.6%, and 21.5±3.6%, respectively (P < 0.01, all comparisons). Secondly, we examined the effect of P. carinii on the function of A549 cells. P. carinii resulted in significant impairment of A549 cell growth, indicating P. carinii adversely affected the function of target lung cells. A P. carinii: A549 cell ratio of 50:1 resulted in 43.5±2.9% inhibition of A549 cell growth (P < 0.001). Additionally, TMCA, which significantly prevented attachment of P. carinii, reversed the impairment of A549 cell growth. These data demonstrate that P. carinii attachment to cultured lung cells can be quantified, is dependent on intact cytoskeletal function and is necessary for impairment of lung cell replication.
KW - Colchicine
KW - Cytochalasin B
KW - Parasite adherence
KW - Pneumocystis carinii
KW - Pneumonia
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U2 - 10.1172/JCI114451
DO - 10.1172/JCI114451
M3 - Article
C2 - 2298914
AN - SCOPUS:0025062619
SN - 0021-9738
VL - 85
SP - 391
EP - 396
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 2
ER -