Intrapulmonary chemotaxins in the normal and in the cyclophosphamide-treated host.
The kinetics of intrapulmonary chemotactic activity and the generation of a pulmonary polymorphonuclear leukocytic (PMN) response during experimental Pseudomonas aeruginosa pneumonia were studied in normal and in cyclophosphamide-treated guinea pigs. In normal animals, chemotactic activity for PMN appeared in airways promptly (2 h) after infection and preceded the influx of PMN to infected airways. Week-long regimens of intraperitoneally administered cyclophosphamide, in dosages of 7.5 mg/kg/day (low-dose) or 15 mg/kg/day (high-dose), resulted in systemic myelosuppression accompanied by a dose-related decrease in recruitment of PMN to infected airways. The chemotactic activity assayed in bronchoalveolar fluids obtained from low-dose-treated animals was not affected by cyclophosphamide. However, chemotactic activity in bronchoalveolar fluids was significantly reduced (p less than 0.01) in animals receiving the high-dose cyclophosphamide regimen. Gel chromatography of bronchoalveolar fluids from infected animals revealed that a high molecular weight (20,000 daltons or greater) and a low molecular weight (5,000 daltons) chemotactic factor were present in normal specimens, and that both were absent from specimens obtained from animals receiving the high-dose treatment. Hemolytically active C5 was detected in infected bronchial fluids, but cyclophosphamide treatment did not reduce amounts of C5 in infected airways. These data suggest that in addition to myelosuppression, cyclophosphamide treatment impairs the capacity for pulmonary inflammation by reducing the normal intrapulmonary chemotactic gradient during infection.
D000818:Animals; D001980:Bronchi / Q000166:cytology / Q000378:metabolism; D002630:Chemotactic Factors / Q000378:metabolism*; D002850:Chromatography, Gel; D003520:Cyclophosphamide / Q000494:pharmacology*; D006168:Guinea Pigs; D008168:Lung / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism; D012016:Reference Values; D007507:Therapeutic Irrigation
D002630:Chemotactic Factors; D003520:Cyclophosphamide