Cytokines affect pseudomonas binding to tracheal cells via a neutrophil-mediated process.
Critical illness is often associated with gram-negative bacterial colonization of the airways, increasing the risk of nosocomial pneumonia. Cytokines, released in response to endotoxin, might contribute to this phenomenon by causing changes in epithelial cell binding of bacteria. To investigate this possibility, human monocytes and hamster pulmonary macrophages were cultured without or with Escherichia coli endotoxin (10 micrograms/ml) for 4 and 24 h. Hamster and human tracheal epithelial cells were treated with supernates from monocyte cultures for 24 h, and subsequent binding of 14C-labeled Pseudomonas aeruginosa to the epithelial cells was measured (percent adherence). In separate experiments, recombinant human (rh) tumor necrosis factor-alpha (TNF-alpha) (25 to 100 ng/ml) and interleukin-1 beta (IL-1 beta) (2,000 to 8,000 pg/ml) were added to hamster monolayers. Neither monocyte supernates nor purified cytokines were toxic to the epithelial cells for up to 48 h. There was no significant change in P. aeruginosa adherence to either hamster or human tracheal epithelial cells after 24 h of exposure to culture supernates from either endotoxin-stimulated human monocytes or hamster macrophages. Similarly, purified rhTNF and rhIL-1 exposure did not increase bacterial adherence. However, when polymorphonuclear leukocytes were coincubated with the monocyte supernates and epithelial cells, P. aeruginosa adherence was significantly increased. Moreover, this effect was enhanced by an epithelial cell-derived substance. Thus, while inflammatory cytokines may participate in enhancing bacterial colonization of the lung in vivo, they do not do so by a direct action on tracheal epithelial cells but can act via a neutrophil-dependent mechanism.
Raoof
S
S
Department of Medicine, Nassau County Medical Center, East Meadow, New York 11554, USA.
Grant
M M
MM
Niederman
M S
MS
Poehlman
M A
MA
Matin
A F
AF
Khan
F A
FA
Fein
A M
AM
D000818:Animals; D001422:Bacterial Adhesion / Q000187:drug effects; D016923:Cell Death; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D006224:Cricetinae; D016207:Cytokines / Q000502:physiology*; D004848:Epithelium / Q000502:physiology; D006801:Humans; D016676:Macrophages, Alveolar; D009000:Monocytes; D009504:Neutrophils / Q000502:physiology*; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity* / Q000502:physiology; D014132:Trachea / Q000166:cytology* / Q000276:immunology / Q000382:microbiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha