产生自由基的骨髓源性调节性细胞：肺部炎症和气道高反应性的强效活化剂和抑制剂
2011/06/17
摘要
哮喘恶化时，气道内的自由基含量显著增加，但这些自由基在哮喘病理生理学中的作用仍然不清楚。我们的研究发现，在实验性过敏性气道炎症的哮喘小鼠肺部，骨髓来源的抑制性细胞是一氧化氮和超氧化物的主要来源，也是气道炎症反应的主要调节细胞。这些细胞自由基的产生依赖于诱导型一氧化氮合成酶(iNOS)、精氨酸酶、烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶的表达。这些自由基控制着这些细胞的促炎和抗炎表现，调节这些细胞肺部浸润的交互反应模式。这些能产生一氧化氮的细胞为Ly-6C(+)Ly-6G(-)细胞，能够抑制T细胞活化、募集调节性T细胞和显著下调抗原诱导的气道高反应性。产生超氧化物的细胞为Ly-6C(-)Ly-6G(+)细胞，具有促炎活性，并以超氧化物依赖性方式增加气道高反应性。一小群Ly-6C(+)Ly-6G(+)细胞也能抑制T细胞反应，但是依赖于iNOS和精氨酸酶。这些骨髓源性调节性细胞可以作为哮喘治疗的重要靶点。
（刘国梁 审校）
Mucosal Immunol. 2011 Apr 6. [Epub ahead of print]
Free radical-producing myeloid-derived regulatory cells: potent activators and suppressors of lung inflammation and airway hyperresponsiveness.
Deshane J, Zmijewski JW, Luther R, Gaggar A, Deshane R, Lai JF, Xu X, Spell M, Estell K, Weaver CT, Abraham E, Schwiebert LM, Chaplin DD.
1] Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA [2] Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA [3] Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Abstract
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.
Mucosal Immunol. 2011 Apr 6. [Epub ahead of print]
哮喘恶化时，气道内的自由基含量显著增加，但这些自由基在哮喘病理生理学中的作用仍然不清楚。我们的研究发现，在实验性过敏性气道炎症的哮喘小鼠肺部，骨髓来源的抑制性细胞是一氧化氮和超氧化物的主要来源，也是气道炎症反应的主要调节细胞。这些细胞自由基的产生依赖于诱导型一氧化氮合成酶(iNOS)、精氨酸酶、烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶的表达。这些自由基控制着这些细胞的促炎和抗炎表现，调节这些细胞肺部浸润的交互反应模式。这些能产生一氧化氮的细胞为Ly-6C(+)Ly-6G(-)细胞，能够抑制T细胞活化、募集调节性T细胞和显著下调抗原诱导的气道高反应性。产生超氧化物的细胞为Ly-6C(-)Ly-6G(+)细胞，具有促炎活性，并以超氧化物依赖性方式增加气道高反应性。一小群Ly-6C(+)Ly-6G(+)细胞也能抑制T细胞反应，但是依赖于iNOS和精氨酸酶。这些骨髓源性调节性细胞可以作为哮喘治疗的重要靶点。
（刘国梁 审校）
Mucosal Immunol. 2011 Apr 6. [Epub ahead of print]
Free radical-producing myeloid-derived regulatory cells: potent activators and suppressors of lung inflammation and airway hyperresponsiveness.
Deshane J, Zmijewski JW, Luther R, Gaggar A, Deshane R, Lai JF, Xu X, Spell M, Estell K, Weaver CT, Abraham E, Schwiebert LM, Chaplin DD.
1] Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA [2] Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA [3] Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Abstract
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.
Mucosal Immunol. 2011 Apr 6. [Epub ahead of print]
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