Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Mucosal Immunol. 2011 Sep;4(5):503-18. doi: 10.1038/mi.2011.16. Epub 2011 Apr 6.
Levels of reactive free radicals are elevated in the airway during asthmatic exacerbations, but their roles in the pathophysiology of asthma remain unclear. We have identified subsets of myeloid-derived suppressor-like cells as key sources of nitric oxide and superoxide in the lungs of mice with evolving experimental allergic airway inflammation and established these cells as master regulators of the airway inflammatory response. The profiles of free radicals they produced depended on expression of inducible nitric oxide synthase (iNOS), arginase, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. These radicals controlled the pro- and anti-inflammatory potential of these cells, and also regulated the reciprocal pattern of their infiltration into the lung. The nitric oxide-producing cells were Ly-6C(+)Ly-6G(-) and they downmodulated T-cell activation, recruited T(reg) cells, and dramatically downregulated antigen-induced airway hyperresponsiveness. The superoxide-producing cells were Ly-6C(-)Ly-6G(+) and they expressed proinflammatory activities, exacerbating airway hyperresponsiveness in a superoxide-dependent fashion. A smaller population of Ly-6C(+)Ly-6G(+) cells also suppressed T-cell responses, but in an iNOS- and arginase-independent fashion. These regulatory myeloid cells represent important targets for asthma therapy.
在哮喘发作期间，气道中活性自由基的水平升高，但它们在哮喘病理生理学中的作用仍不清楚。我们已经确定了髓样来源的抑制性细胞亚群作为在进行性实验性变应性气道炎症的小鼠肺部中一氧化氮和超氧化物的关键来源，并将这些细胞确立为气道炎症反应的主要调节者。它们产生的自由基谱取决于诱导型一氧化氮合酶 (iNOS)、精氨酸酶和烟酰胺腺嘌呤二核苷酸磷酸 (NADPH) 氧化酶的表达。这些自由基控制这些细胞的促炎和抗炎潜力，并调节它们在肺部中的浸润的相互模式。产生一氧化氮的细胞是 Ly-6C(+)Ly-6G(-)，它们下调 T 细胞激活、募集 T(reg)细胞，并显著下调抗原诱导的气道高反应性。产生超氧化物的细胞是 Ly-6C(-)Ly-6G(+)，它们表达促炎活性，以超氧化物依赖的方式加重气道高反应性。较小比例的 Ly-6C(+)Ly-6G(+)细胞也抑制 T 细胞反应，但以 iNOS 和精氨酸酶非依赖性方式。这些调节性髓样细胞是哮喘治疗的重要靶点。
