Lung epithelial cell-released nitric oxide protects against PMN-mediated cell injury.
A calcium-independent type II nitric oxide (NO) synthase has been localized in lung epithelial cells; however, the function of NO. released by epithelial cells is unclear. We hypothesized that epithelial-derived NO may affect the interactions between polymorphonuclear neutrophils (PMN) and the alveolar epithelium and studied PMN adhesion and cytotoxicity to lung epithelial cells. A dose- and time-dependent production of NO. by L2 cells can be induced by a mixture of inflammatory mediators (cytomix) containing lipopolysaccharide, tumor necrosis factor-alpha, and interferon-gamma. Increased NO. production by L2 cells was associated with decreased 51Cr release by the epithelial cells after they were incubated with activated PMN. Addition of NG-monomethyl-L-arginine or oxyhemoglobin reversed the protective effects of cytomix, suggesting that increased NO. production by L2 cells was responsible for the decreased 51Cr release. However, PMN adhesion and intercellular adhesion molecule-1, a major adhesion molecule involved in PMN adhesion to epithelium, were increased by cytomix. We conclude that NO. released by lung epithelial cells was involved in protecting epithelial cells from PMN-mediated cytotoxicity. NO.-mediated protection of lung epithelial cells occurred in spite of PMN adhesion being increased, suggesting that reduced adhesion is not required for NO.-mediated inhibition of PMN cytotoxicity.
Su
W Y
WY
Department of Medicine, Duke University, Durham, North Carolina 27710, USA.
Day
B J
BJ
Kang
B H
BH
Crapo
J D
JD
Huang
Y C
YC
Chang
L Y
LY
D000818:Animals; D002448:Cell Adhesion; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D051381:Rats
D016207:Cytokines; D009573:Nitrites; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase