Effects of hemorrhage and resuscitation on bacterial antigen-specific pulmonary plasma cell function.
METHODS
Nosocomial pneumonia is frequent after hemorrhage and trauma, and often contributes to multiple organ system failure, morbidity, and mortality in this setting. Although the percentages and numbers of resting pulmonary B cells (clonal precursors) able to be stimulated to produce antibodies to bacterial antigens are markedly decreased after hemorrhage, the effects of hemorrhage on the pulmonary plasma cells actually producing antibody to bacterial antigens have not been examined. To investigate this question, mice were bled 30% blood volume, then resuscitated with the shed blood 1 hr later. At predetermined times after hemorrhage, the mice were intranasally immunized with liposomes containing the bacterial polysaccharide antigen levan (from Aerobacter levanicum). One week later, lung lavages were performed to measure bacterial antigen-specific secretory immunoglobulin A (sIgA) titers and the numbers of intraparenchymal pulmonary plasma cells producing antibody against the bacterial antigen were determined.


RESULTS
Reduced numbers of pulmonary plasma cells producing antibody against the immunizing bacterial polysaccharide antigen were found between 1 and 14 days after blood loss, and titers of bacterial antigen-specific secretory IgA were decreased for greater than 2 wks after hemorrhage. The importance of these abnormalities in pulmonary B-cell function was demonstrated by an increased susceptibility to Pseudomonas aeruginosa pneumonia in mice infected 4 days after hemorrhage, when bacterial antigen-specific pulmonary plasma cell numbers were at their lowest point. Resuscitated mice showed the same increased susceptibility to P. aeruginosa pneumonia as did hemorrhaged but unresuscitated animals.


CONCLUSIONS
Hemorrhage, even if resuscitated, results in alterations in bacterial antigen-specific pulmonary B-cell function and secretory IgA production that are profound, long lasting, and associated with increased susceptibility to infection at this mucosal surface. Because these effects on pulmonary B-cell function do not occur immediately after hemorrhage, immunization techniques able to enhance bacterial antigen-specific secretory IgA titers at pulmonary surfaces may be able to increase resistance to nosocomial pneumonia if administered shortly after injury and blood loss.
Department of Medicine, University of California, Los Angeles Medical Center 90024.
A
A
Robinson
E
E
Abraham
D000818:Animals; D000942:Antigens, Bacterial / Q000302:isolation & purification*; D006470:Hemorrhage / Q000276:immunology / Q000628:therapy*; D007071:Immunoglobulin A, Secretory / Q000276:immunology / Q000302:isolation & purification; D008171:Lung Diseases / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D011550:Pseudomonas aeruginosa; D012151:Resuscitation
D000942:Antigens, Bacterial; D007071:Immunoglobulin A, Secretory; D011135:Polysaccharides, Bacterial