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Pseudomonas aeruginosa is one of the major causative agents of mortality and morbidity in hospitalized patients due to a multiplicity of virulence factors associated with both chronic and acute infections. Acute P. aeruginosa infection is primarily mediated by planktonic bacteria expressing the type III secretiun system (TTSS), a surface-attached needle-like complex that injects eytotoxins directly into eukaryotic cells, causing cellular damage. Lipopolysaccharide (LPS) is the principal surface-associated virulence factor of P. aeruginosa. This molecule is known to undergo structural modification (primarily alterations in the A- and B-band O antigen) in response to changes in the mode of life (e.g., from biofilm to planktonic). Given that LPS exhibits structural plasticity, we hypothesized that the presence of LPS lacking O antigen would facilitate enkaryotic intoxication and that a correlation between the LPS O-antigen serotype and TTSS-mediated cytotoxicity would exist. Therefore, strain PAO1 ([A.sup.+] [B.sup.+] O-antigen serotype) and isogenic mutants with specific O-antigen defects ([A.sup.+] [B.sup.-], [A.sup.-] [B.sup.+], and [A.sup.-] [B.sup.-]) were examined for TTSS expression and cytotoxicity. A strong association existed in vitro between the absence of the large, structured B-band O antigen and increased cytotoxicity of these strains. In vivo, all three LPS mutant strains demonstrated significantly increased lung injury compared to PAO1. Clinical strains lacking the B-band O antigen also demonstrated increased TTSS secretion. These results suggest the existence of a cooperative association between LPS O-antigen structure and the TTSS in both laboratory and clinical isolates of P. aeruginosa.

The effects of NO inhalation coupled on lung barriers that were exposed to sublethal O2 concentrations were analyzed in isolated-lung perfused models. Analysis of NO inhalation in Sprague-Dawley rats exposed to sublethal O2 exhibited reduced O2-induced lung endothelial and alveolar epithelial injury. The inhibitory effects of NO on hyperoxia-induced lung damage exhibited the protective effect of the compound on the barrier function of lung endothelium and alveolar endothelium.

Exotoxin A is an exoproduct of Pseudomonas aeruginosa that can form transmembrane pores in phospholipid bilayers. However, its effect on fluid reabsorption in the airspaces of the lung has not been elucidated. To determine this effect, exotoxin A was instilled in varying doses in the lung epithelium. Results showed a dose-dependent increase in the fluid transport across the lung epithelium. This uptake was shown to be dependent on the uptake of sodium across the epithelium. It is concluded that exotoxin A induces fluid removal from the air spaces by the lung epithelium.

The possible neutrophil recruitment and degranulation function of the neutrophil-activation peptide-2 (NAP-2) in the lungs of persons afflicted with adult respiratory distress syndrome or congenitive heart failure (CHR) was examined. A radioimmunoassay was used to measure NAP-2 precursors plus NAP-2 in lung fluids and plasmas. High- performance liquid chromatography separated NAP-2 from its precursors. The migration of neutrophils into the lungs of patients with CHF or ARDS was established.