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Lung injury during LPS-induced inflammation occurs independently of the receptor P2Y1

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Abstract

Disruption of the lung endothelial and epithelial barriers during acute inflammation leads to excessive neutrophil migration. It is likely that activated platelets promote pulmonary recruitment of neutrophils during inflammation, and previous studies have found that anti-platelet therapy and depletion of circulating platelets have lung-protective effects in different models of inflammation. Because ADP signaling is important for platelet activation, I investigated the role of the ADP-receptor P2Y1, a G protein-coupled receptor expressed on the surface of circulating platelets, during lipopolysaccharide (LPS)-induced inflammation and lung injury in P2Y1-null and wild-type mice. Systemic inflammation was induced by a single intraperitoneal dose of LPS (3 mg/kg), and the mice were analyzed 24 h posttreatment. The data show that the LPS-induced inflammation levels were comparable in the P2Y1-null and wild-type mice. Specifically, splenomegaly, counts of circulating platelets and white blood cells (lymphocytes and neutrophils), and assessments of lung injury (tissue architecture and cell infiltration) were similar in the P2Y1-null and wild-type mice. Based on my results, I conclude that lung injury during LPS-induced inflammation in mice is independent of P2Y1 signaling. I propose that if a blockade of purinergic signaling in platelets is a potential lung-protective strategy in the treatment of acute inflammation, then it is more likely to be a result of the disruption of the signaling pathway mediated by P2Y12, another G protein-coupled receptor that mediates platelet responses to ADP.

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Acknowledgments

I would like to thank Satya P. Kunapuli for providing the P2Y1-null mice. This work was supported by the American Heart Association Grant 16SDG26980003 (to E.L.).

Authorship

E.L. designed and conducted the experiments described, carried out the data analysis and statistical tests presented, interpreted the results, and wrote the manuscript.

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Authors and Affiliations

  1. Sol Sherry Thrombosis Research Center and Center for Inflammation, Translational and Clinical Lung Research, Temple University School of Medicine, Temple University Hospital, Temple University, 3420 N. Broad Street, Philadelphia, PA, 19140, USA

    Elisabetta Liverani

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  1. Elisabetta Liverani
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Correspondence to Elisabetta Liverani.

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All procedures for the care and handling of the animals adhered to the National Institutes of Health standards and were approved by the Institutional Animal Care and Use Committee at Temple University School of Medicine (Philadelphia, PA).

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The author declares that she has no conflict of interest.

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Liverani, E. Lung injury during LPS-induced inflammation occurs independently of the receptor P2Y1 . Purinergic Signalling 13, 119–125 (2017). https://doi.org/10.1007/s11302-016-9543-2

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