The cellular pulmonary host defenses (alveolar macrophages and recruited polymorphonuclear leukocytes, PMNs) are important in host defense against invading microorganisms; bronchopulmonary infection is a significant threat to patients with adult respiratory distress syndrome (ARDS). The establishment of ARDS, as well as the prognosis and outcome from ARDS and infection are interrelated. We hypothesize that the cellular pulmonary host defenses are abnormal in patients with ARDS and due to predisposing insults may predispose these patients to infection and progressive ARDS or to nosocomial infection following ARDS. To evaluate this hypothesis, we will utilize the in dog model of ARDS (acid aspiration and sepsis models) and the isolated perfused lung preparation to evaluate the antimicrobial activity and metabolic/structural responses of alveolar macrophages, PMNs (pulmonary), peripheral blood monocytes and PMNs in ARDS models compared to controls. The antimicrobial activity to be evaluated will include: phagocytosis and killing of Staph. aureus, E. coli, Pseudomonas aeruginosa, and Candida albicans. The oxidative metabolic burst, cytochemical, ultrastructural and surface membranes will be evaluated in ARDS verus control cells. Evaluation of the mechanisms of oxidative killing will follow the demonstration of antimicrobial patterns and potential defects. The long-term goal would allow for modifications, manipulations and/or prevention of circumstances in cellular defense to protect the lung from the establishment of ARDS or nosocomial pneumonia following ARDS.
| Jacobs, R F; Dorsey, D R; Tryka, A F et al. (1988) Pulmonary macrophage antimicrobial activity in canine endotoxin shock and lung injury. Exp Lung Res 14:359-74 |
| Tabor, D R; Burchett, S K; Jacobs, R F (1988) Enhanced production of monokines by canine alveolar macrophages in response to endotoxin-induced shock. Proc Soc Exp Biol Med 187:408-15 |
| Balk, R A; Jacobs, R F; Tryka, A F et al. (1988) Effects of ibuprofen on neutrophil function and acute lung injury in canine endotoxin shock. Crit Care Med 16:1121-7 |
| Balk, R A; Jacobs, R F; Tryka, A F et al. (1988) Low dose ibuprofen reverses the hemodynamic alterations of canine endotoxin shock. Crit Care Med 16:1128-31 |
| Tabor, D R; Kiel, D P; Jacobs, R F (1987) Receptor-mediated ingestion responses by lung macrophages from a canine model of ARDS. J Leukoc Biol 41:539-43 |
| Jacobs, R F; Kiel, D P; Balk, R A (1986) Alveolar macrophage function in a canine model of endotoxin-induced lung injury. Am Rev Respir Dis 134:745-51 |
