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Editorial
Friend or foe? The dual role of neutrophils in lung injury and repair
  1. Frances S Grudzinska,
  2. Elizabeth Sapey
  1. Institute of Inflammation and Ageing, Queen Elizabeth Hospital, University of Birmingham, Birmingham, UK
  1. Correspondence to Dr Elizabeth Sapey, Institute of Inflammation and Ageing, Queen Elizabeth Hospital, University of Birmingham, Birmingham B15 2TT, UK; e.sapey{at}bham.ac.uk

https://doi.org/10.1136/thoraxjnl-2017-211253

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    Studies describing the role of neutrophils in acute lung injury (ALI) show divergent results. Some support a pivotal role for neutrophils in the development of lung injury, with improvements in outcomes following inhibition of neutrophil recruitment or their granular contents. Others describe poorer outcomes in patients with neutropenia and no improvements in clinical outcomes or inflammatory biomarkers following interventions which target neutrophils. This has led to uncertainty about whether neutrophils are a therapeutic target in this condition. The recent publication by Blázquez-Prieto et al provides some insight into why different studies may vary in outcome. It describes increased inflammation and a poorer recovery in a murine model where neutrophils are depleted 24 hours after a ventilator-induced lung injury (VILI), and links tissue repair to the sustained activity of neutrophil-derived matrix metalloproteinase (MMP)-9 in cellular, animal and human studies. These data suggest the timing of targeting neutrophils may be critical for improving outcomes in ALI. This editorial explores the evidence for this finding and discusses heterogeneous neutrophil populations in disease and the role of MMP-9 in tissue repair. 

    Our current understanding of the pathogenesis of ALI includes a paradox which incorporates the following four pieces of evidence.

    First, in human and animal studies, neutrophil numbers in bronchoalveolar lavage fluid (BALF) correlate with ALI severity and are predictive of mortality.1 Furthermore, there is evidence of increased neutrophil proteinase (especially neutrophil elastase) and oxidant2 activity in ALI which correlate with the severity of the clinical syndrome. This suggests that neutrophils are centrally implicated in the onset and progression of ALI, where endothelial and epithelial injuries are associated with microvascular permeability, increased tissue oedema and an early accumulation of activated neutrophils to the lung.

    Second, in animal models of ALI, reducing neutrophil accumulation to the lung (eg, by targeting CXCR2) or/and inhibiting the …

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    Footnotes

    • Contributors FSG cowrote the article and helped with figure preparation. ES cowrote and finalised the article and completed the figure preparation.

    • Competing interests ESG reports grants from Medical Research Council, grants from British Lung Foundation, grants from NIHR, grants from Alpha 1 Foundation, grants from Wellcome Trust, outside the submitted work.

    • Provenance and peer review Commissioned; externally peer reviewed.

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