INTRATRACHEAL ADMINISTRATION OF IMMUNOGLOBULINS FOR THE PREVENTION OF PSEUDOMONAS AERUGINOSA PNEUMONIA IN MICE
Abstract
This study describes a unique approach to the prevention of gram negative bacterial pneumonia. It dealt with the following topics: Establishment of pneumonia in mice by intratracheal inoculation with a mucoid strain of Pseudomonas aeruginosa; successful prevention of pneumonia and death in infected mice by prior intratracheal instillation of antiserum and immune globulins; and characterization of the protective activity of immune globulins by histopathological observation, lung lavage, and opsonophagocytic assays. Intratracheal inoculation was accomplished using a blunt tipped feeding needle inserted through the larynx. Instillation of 5 x 10('8) colony forming units of a cystic fibrosis-derived mucoid strain of P. aeruginosa (PA 1433) produced an acute pneumonia in all mice within 24 hours. The pneumonia was non-bacteremic, and infected animals died within 36-48 hours after inoculation. Rabbit antiserum, produced against a heat-killed whole cell PA 1433 bacterin, and fractionated globulins, were effective in preventing morbidity and mortality when given intratracheally 1, 3, or 5 days before bacterial challenge. The greatest degree of protection, measured by survival and bacterial clearance studies, was seen when globulins were administered 3 days before infection. Intratracheal administration of normal rabbit serum afforded little or no protection against subsequent bacterial challenge. Analysis of lung lavage samples taken after administration of globulins revealed a marked influx of neutrophils after 1 day in mice receiving both normal and immune globulins. Three days after instillation, there were more macrophages in lavage samples taken from mice receiving immune globulins. Using in vitro opsonophagocytic assays, both alveolar macrophages and neutrophils were shown to be effective in killing PA 1433 in the presence of immune globulins. Thus, the mechanism for the observed protective activity of immune globulins is likely due to recruitment of phagocytic cells into the lung, and opsonization of the bacteria for subsequent phagocytosis.
Degree
Ph.D.
Subject Area
Microbiology
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