The effects of cyclosporine and dexamethasone on an alveolar macrophage cell line (NR8383).
Lung infections are a major source of morbidity and mortality in recipients of lung transplants. Prominent among the pathogens that cause pneumonias in these subjects are gram-negative bacilli, particularly Pseudomonas strains. One important reason that bacteria infect the lungs of these patients is that pulmonary defenses are impaired by the drugs used to prevent transplant rejection. Using a rat alveolar macrophage cell line (NR8383), we measured the effects of exposure (24 hr) to cyclosporine and dexamethasone (DEX) on the ability of these cells to (1) kill Pseudomonas aeruginosa (Pa); (2) produce H2O2; and (3) release tumor necrosis factor. We found that the bactericidal activity against unopsonized or opsonized Pa of NR8383 cells was unaltered by CsA (0.1, 0.5, or 1 micrograms/ml), DEX (10(-6) M), or CsA + DEX (0.5 micrograms/ml + 10(-6) M, respectively). Likewise, LPS-induced TNF release, and zymosan A and Pa-induced H2O2 production were unaltered by CsA (0.1 or 1 microgram/ml). In contrast, H2O2 production and TNF release were decreased by about 50% and 90%, respectively, by DEX exposure (10(-6) M). Thus, while DEX but not CsA decreased TNF release and H2O2 production in NR8383 cells, bactericidal activity against Pa was unaffected. One explanation for these results is that decreases in TNF or H2O2 of the magnitude we observed do not impair bactericidal activity against Pa; however, an alternative explanation is that Pa are killed by NR8383 cells through other mechanisms. Interpretation of these results must take into consideration the fact that macrophages from different species and tissues may respond differently to various stimuli.
Hidalgo
H A
HA
Department of Pediatrics, University of Texas Health Science Center, San Antonio 78284.
Helmke
R J
RJ
German
V F
VF
Mangos
J A
JA
D000818:Animals; D001770:Blood Bactericidal Activity / Q000187:drug effects; D002460:Cell Line; D016572:Cyclosporine / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D016572:Cyclosporine; D006861:Hydrogen Peroxide