NK cells regulate CXCR2+ neutrophil recruitment during acute lung injury

• DOI: 10.1189/jlb.3a0516-227r
• Publication Date: 2016-09-07T03:02:26Z
• Authors: Sandra Hoegl; Heidi Ehrentraut; Kelley S Brodsky; Francisco Victorino; Lucy Golden-Mason; Holger K Eltzschig; Eóin N McNamee
• Keywords: Neutrophilia; Infiltration (HVAC); CXCL1; Adoptive Cell Transfer; Pathogenesis

Abstract A critical step in the pathogenesis of acute lung injury (ALI) is excessive recruitment polymorphonuclear neutrophils (PMNs) into lungs, causing significant collateral tissue damage. Defining molecular and cellular steps that control neutrophil infiltration activation during ALI therefore important therapeutic relevance. Based on previous findings implicating transcription factor Tbet mucosal Th1-inflammation, we hypothesized a detrimental role for ALI. In line with our hypothesis, initial studies endotoxin-induced revealed marked protection Tbet−/− mice, including attenuated neutrophilia compared to WT counterparts. Surprisingly, subsequent identified natural killer (NK) cells as major source pulmonary addition, chemokine screen suggested mature Tbet+ NK-cells are production CXCL1 -2, thereby contributing PMN recruitment. Indeed, both NK-cell Ab depletion adoptive transfer provide evidence NK orchestration Taken together, these identify novel initiating early events noninfectious inflammation.