Regulatory Effects of iNOS on Acute Lung Inflammatory Responses in Mice

Abstract

The role of endogenous NO in the regulation of acute lung injury is not well defined. We investigated the effects of inducible nitric oxide synthase (iNOS) and endothelial NOS (eNOS) on the acute inflammatoryThere is abundant evidence that lung inflammatory injury, occurring after a variety of insults, is due to activation of lung phagocytic cells, which produce numerous chemokines (reviewed).1 CXC chemokines are thought to attract neutrophils into the lung, while CC chemokines attract lymphocytes and monocytes and also have the ability to activate macrophages.2 It is well known that a variety of lung cells other than phagocytic cells have the ability to generate cytokines and chemokines.3 For inflammatory reactions that lead to injury, the role of NO is controversial, with evidence for pro-inflammatory as well as antiinflammatory effects. 4 In various lung injury models, neutrophil recruitment, cytokine production, and oxygen radical production were reduced in the presence of either inhaled NO or exogenous NO donors, suggesting a beneficial role for NO in acute lung injury. [5][6][7] In contrast, a decrease in lung permeability and neutrophil recruitment was shown in various models of lung injury using NO synthase (NOS) inhibitors, suggesting a harmful effect of NO on lung injury. 8 -10

Inhibition of the MAP kinase ERK protects from lipopolysaccharide-induced lung injury

“…It is well known that LPS injures lung endothelial and epithelial cells and enhances lung permeability [27]. Recently it has been shown that acute lung injury can be attenuated by reduction of lung hyperpermeability [28]. In this study we observed that endotoxin inhalation led to elevated albumin levels in bronchoalveolar lavage, which is marker of increased lung epithelial permeability.…”

Acute and persisting Th2-like immune response after fractionated colorectal γ-irradiation

“…The present study revealed a biphasic pattern of iNOS expression: early overexpression during the fractionated protocol, followed by delayed suppression, seen at 6 mo. In particularly, iNOS regulates chemokine expression involved in leukocyte (especially neutrophil) trafficking: the absence of iNOS enhances lung inflammatory responses, associated with increased production of MCP-1 by endothelial cells and macrophages [26] . Reports about iNOS regulation of the production of this CC chemokine are contradictory.…”

Comparison of Effects of Nitric Oxide Synthase (NOS) Inhibitors on Plasma Nitrite/Nitrate Levels and Tissue NOS Activity in Septic Organs

“…iNOS gene-deficient mice injected with lipopolysaccharide (LPS) have been reported to show an increased resistance to lethality but a decreased resistance to bacterial inoculation (12,29). It has been reported that iNOS-derived NO suppresses tissue damage in acute lung injury; it acts to block the generation of chemokines (23) or inhibits sepsis-induced pulmonary apoptosis (22). Thus, iNOS-derived NO has both a beneficial effect (defence against infectious Numerous studies have been done concerning the relationship between the benefits and costs of inhibiting NO production in septic models (5,10,26,28,30).…”