First Author | Potera RM | Year | 2019 |
Journal | Inflammation | Volume | 42 |
Issue | 1 | Pages | 185-198 |
PubMed ID | 30288635 | Mgi Jnum | J:295691 |
Mgi Id | MGI:6454234 | Doi | 10.1007/s10753-018-0883-7 |
Citation | Potera RM, et al. (2019) Alveolar Macrophage Chemokine Secretion Mediates Neutrophilic Lung Injury in Nox2-Deficient Mice. Inflammation 42(1):185-198 |
abstractText | Acute lung injury (ALI), developing as a component of the systemic inflammatory response syndrome (SIRS), leads to significant morbidity and mortality. Reactive oxygen species (ROS), produced in part by the neutrophil NADPH oxidase 2 (Nox2), have been implicated in the pathogenesis of ALI. Previous studies in our laboratory demonstrated the development of pulmonary inflammation in Nox2-deficient (gp91(phox-/y)) mice that was absent in WT mice in a murine model of SIRS. Given this finding, we hypothesized that Nox2 in a resident cell in the lung, specifically the alveolar macrophage, has an essential anti-inflammatory role. Using a murine model of SIRS, we examined whole-lung digests and bronchoalveolar lavage fluid (BALf) from WT and gp91(phox-/y) mice. Both genotypes demonstrated neutrophil sequestration in the lung during SIRS, but neutrophil migration into the alveolar space was only present in the gp91(phox-/y) mice. Macrophage inflammatory protein (MIP)-1alpha gene expression and protein secretion were higher in whole-lung digest from uninjected gp91(phox-/y) mice compared to the WT mice. Gene expression of MIP-1alpha, MCP-1, and MIP-2 was upregulated in alveolar macrophages obtained from gp91(phox-/y) mice at baseline compared with WT mice. Further, ex vivo analysis of alveolar macrophages, but not bone marrow-derived macrophages or peritoneal macrophages, demonstrated higher gene expression of MIP-1alpha and MIP-2. Moreover, isolated lung polymorphonuclear neutrophils migrate to BALf obtained from gp91(phox-/y) mice, further providing evidence of a cell-specific anti-inflammatory role for Nox2 in alveolar macrophages. We speculate that Nox2 represses the development of inflammatory lung injury by modulating chemokine expression by the alveolar macrophage. |