NADPH Oxidase-dependent Activation Of CD4+ T Cells Modulates Macrophage And Alveolar Epithelial Cell Activation During Lung Ischemia-reperfusion Injury

Sharma, Ashish K.; Hajzus, Vanessa A.; Kazemi, Ali; Krön, Irving L.; Laubach, Victor E.

doi:10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a1095

Cited by 1 publication

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is possible that the increase (recruitment) in the number of IL-17A-producing iNKT cells, and not the induction of IL-17A per se, is the main stimulus for IL-17-mediated IR injury. However, we believe that iNKT cells do significantly produce IL-17A in response to IR, which is supported by preliminary data demonstrating that production of IL-17A is significantly induced by primary CD4 1 T cells when exposed to acute hypoxia/reoxygenation (38).…”

Section: Discussionsupporting

confidence: 63%

Natural Killer T Cell–derived IL-17 Mediates Lung Ischemia–Reperfusion Injury

Sharma¹,

LaPar²,

Zhao³

et al. 2011

Am J Respir Crit Care Med

Self Cite

110

133

View full text Add to dashboard Cite

Rationale: We recently implicated a role for CD4 1 T cells and demonstrated elevated IL-17A expression in lung ischemia-reperfusion (IR) injury. However, identification of the specific subset of CD4 1 T cells and their mechanistic role in IR injury remains unknown. Objectives: We tested the hypothesis that invariant natural killer T (iNKT) cells mediate lung IR injury via IL-17A signaling. Methods: Mice underwent lung IR via left hilar ligation. Pulmonary function was measured using an isolated lung system. Lung injury was assessed by measuring edema (wet/dry weight) and vascular permeability (Evans blue dye). Inflammation was assessed by measuring proinflammatory cytokines in lungs, and neutrophil infiltration was measured by immunohistochemistry and myeloperoxidase levels. Measurements and Main Results: Pulmonary dysfunction (increased airway resistance and pulmonary artery pressure and decreased pulmonary compliance), injury (edema, vascular permeability), and inflammation (elevated IL-17A; IL-6; tumor necrosis factor-a; monocyte chemotactic protein-1; keratinocyte-derived chemokine; regulated upon activation, normal T-cell expressed and secreted; and neutrophil infiltration) after IR were attenuated in IL-17A 2/2 and Rag-1 2/2 mice. Anti-IL-17A antibody attenuated lung dysfunction in wildtype mice after IR. Reconstitution of Rag-1 2/2 mice with wild-type, but not IL-17A 2/2 , CD4 1 T cells restored lung dysfunction, injury, and inflammation after IR. Lung dysfunction, injury, IL-17A expression, and neutrophil infiltration were attenuated in Ja18 2/2 mice after IR, all of which were restored by reconstitution with wild-type, but not IL-17A 2/2 , iNKT cells. Flow cytometry and enzyme-linked immunosorbent spot assay confirmed IL-17A production by iNKT cells after IR.Conclusions: These results demonstrate that CD4 1 iNKT cells play a pivotal role in initiating lung injury, inflammation, and neutrophil recruitment after IR via an IL-17A-dependent mechanism.

show abstract

Section: Discussionsupporting

confidence: 63%