Inhaled NO prevents IL-1-induced neutrophil accumulation and associated acute edema in isolated rat lungs.
We determined previously that inhaled nitric oxide (NO) prevented oxidant-dependent capillary leak in isolated rat lungs perfused with human neutrophils and fMLP via a mechanism that was independent of vasodilatation. In the present investigation we determined that inhaled NO (50 ppm) prevented oxidant-dependent acute capillary leak (as reflected by weight gain and Ficoll retention) in isolated rat lungs given human recombinant interleukin-1 alpha (IL-1, 50 ng) intratracheally and perfused with human neutrophils. Inhaled NO also reduced neutrophil migration from the vascular to the airway compartment (as reflected by lung lavage fluid neutrophil numbers and levels of myeloperoxidase), in rats given IL-1 intratracheally and perfused with neutrophils. However, NO did not prevent IL-1-mediated increases in lung lavage levels of cytokine-induced neutrophil chemoattractant (CINC), a potent chemokine produced by alveolar macrophages and other resident cells that mediates IL-1-induced neutrophil infiltration in vivo. We conclude that inhaled NO prevented neutrophil migration and leak caused by intratracheal administration of IL-1 and neutrophil perfusion in isolated rat lungs. We speculate that NO directly inhibits neutrophil responsivity during lung inflammation, a premise that is consistent with the known effects of NO on neutrophil function in vitro. This study provides further evidence that inhaled NO may have important anti-inflammatory as well as vasodilator effects in acute lung injury.
Guidot
D M
DM
Atlanta Department of Veterans Affairs Medical Center, Georgia 30033, USA.
Hybertson
B M
BM
Kitlowski
R P
RP
Repine
J E
JE
D000208:Acute Disease; D000280:Administration, Inhalation; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002465:Cell Movement / Q000187:drug effects; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000032:analysis; D006133:Growth Substances / Q000032:analysis; D006801:Humans; D066298:In Vitro Techniques; D007267:Injections; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D008168:Lung / Q000473:pathology*; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology*; D010477:Perfusion; D011654:Pulmonary Edema / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D014132:Trachea
C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C513297:Cxcl1 protein, rat; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D011994:Recombinant Proteins; D009569:Nitric Oxide