Contribution of macrophages to pulmonary nitric oxide production in septic shock.
Bacterial lipopolysaccharide (LPS) is known to induce the expression of inducible nitric oxide synthase (iNOS) in the lung and to lead to increased pulmonary nitric oxide (NO) production. The contribution of various pulmonary cells to this phenomenon remains unclear. In this study, we used gadolinium chloride, a blocker of macrophage activation, to assess the role of macrophages in LPS-induced pulmonary NO production. Anesthetized, mechanically ventilated rats were injected with either saline or LPS (Escherichia coli endotoxin) and studied for 5 h. Two other groups of rats were pretreated 24 h earlier with gadolinium chloride. Unlike control rats, rats injected with LPS showed a progressive decline in arterial pressure and a several-fold rise in lung iNOS activity and exhaled NO concentration. Large numbers of alveolar macrophages also expressed iNOS after LPS injection. Gadolinium chloride pretreatment eliminated the rise in lung iNOS activity and protein expression and significantly attenuated the increase in pulmonary exhaled NO product, but it had no effect on arterial pressure. Fewer numbers of alveolar macrophages expressed iNOS protein after gadolinium pretreatment. We conclude that macrophage activation plays a critical role in enhancing NO production in the respiratory system, but it is of less importance in mediating hemodynamic alterations of acute endotoxemia.
Fujii
Y
Y
Critical Care Division, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada.
Goldberg
P
P
Hussain
S N
SN
D000818:Animals; D001794:Blood Pressure; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004926:Escherichia coli; D005682:Gadolinium / Q000494:pharmacology; D015151:Immunoblotting; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000201:enzymology / Q000378:metabolism*; D008262:Macrophage Activation / Q000187:drug effects; D016676:Macrophages, Alveolar / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000378:metabolism* / Q000503:physiopathology
D008070:Lipopolysaccharides; D009569:Nitric Oxide; D005682:Gadolinium; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C038958:gadolinium chloride