Effector mechanisms of intestinally induced immunity to Pseudomonas aeruginosa in the rat lung: role of neutrophils and leukotriene B4.

摘要

This paper investigates the effector mechanisms of immune clearance in the lungs of rats immunized against mucoid Pseudomonas aeruginosa. After the gut-associated lymphoid tissue was primed and after a subsequent pulmonary challenge with live bacteria, significantly accelerated bacterial clearances from the lung and raised levels of anti-P. aeruginosa antibodies in sera (immunoglobulin G [IgG], IgA, and IgM) and bronchoalveolar lavages (IgG and IgA) were observed for all immune animals. These changes were associated with enhanced recruitment, chemotaxis, chemokinesis, phagocytic indices, and chemiluminescence of pulmonary polymorphonuclear neutrophils (PMN). In the alveolar spaces of immune animals, an increase in the level of PMN recruitment was not associated with higher levels of leukotriene B4 (LTB4). In contrast, in nonimmune animals that were intratracheally infected with P. aeruginosa, the levels of recruitment and activity of alveolar PMN were lower than those in immune rats but PMN infiltration correlated with a significant increase in the synthesis of LTB4 in the alveolar space. In pulmonary tissue, LTB4 synthesis for both groups was elevated. These findings suggest that accelerated clearance of mucoid P. aeruginosa from the lungs of intestinally immunized rats is due at least in part to factors that induce the enhancement of PMN recruitment and activity in the alveolar space. The mediators that regulate this enhanced response remain unknown but do not seem to include LTB4. The high levels of LTB4 measured in the bronchoalveolar lavages and pulmonary tissues from nonimmune animals infected with live bacteria implicate LTB4 as an important amplifier of the inflammatory response during acute pulmonary infections with mucoid P. aeruginosa in unimmunized hosts.