A B S T R A C T We have investigated the effect of hypocomplementemia on early pulmonary clearance of four species of bacteria. The experiments were performed in an inbred animal model to minimize immunologic variability. Complement was depleted by cobra venom factor, and activity in serum was monitored with a phagocytic assay. Bacterial specific antibodies were examined by an indirect radioimmunoassay, and animals with high levels of activity were excluded from analysis.4 h after aerosolization with Streptococcus pneumoniae, complement-depleted animals had cleared only 75% of the initial number of organisms, whereas saline-treated controls cleared 91% (P < 0.01). Aerosolization with Pseudomonas aeruginosa was followed at 4 h by a twofold greater growth of organisms in the complement-depleted animals (446% of original deposition) as compared to the saline-treated controls (211% of original deposition) (P < 0.02). Clearance of Klebsiella pneumoniae and Staphylococcus aureus were similar in complement-depleted animals and saline-treated controls.These experiments suggest that hypocomplementemia predisposes to bacterial pneumonia and may explain the high incidence of pulmonary infections in patients having impaired complement activity. Our results further indicate that varying defense mechanisms may be involved with clearing the lung of differing bacterial species.
When two sets of phagocytic cells participate simultaneously in the inflammatory process and bacterial killing, the relative contribution of each cell type is difficult to ascertain. The use of cell-specific antibody will permit selective depletion of one phagocyte population. We describe an experimental model of granulocytopenia which utilizes the immunoglobulin G fraction of an antigranulocyte serum. This material markedly depleted circulating polymorphonuclear leukocytes (PMN); within 2 h after injection of antigranulocyte globulin, PMN counts were at 19% of original levels and remained significantly depressed for 24 h. Granulocyte recruitment was also impaired, with only 5 x 103 PMN appearing in the lungs in response to an aerosol of Klebsiella, compared to 4.17 x i05 PMN in control animals (P < 0.01). Most importantly, alveolar macrophages retained normal viability (97% versus 94% for control value, P not significant), normal phagocytic function, and normal bactericidal capacity. Antigranulocyte globulin is thus a valuable tool for the study of bacterial defense mechanisms.
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