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Macrophages play an essential role in trauma-induced sterile inflammation and tissue repair

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Abstract

Severe trauma is accompanied by a profound activation of the immune system. Patients with polytrauma develop systemic inflammatory response syndrome (SIRS) and often sepsis, which contributes substantially to high mortality of this condition. On a cellular level, necrosis and loss of plasma membrane integrity lead to the release of endogenous “damage-associated molecular patterns” (DAMPs) as danger signals, which in turn activate innate immune cells. Inflammation that occurs in the absence of invading pathogens has been termed sterile inflammation and trauma with tissue damage represents an acute form of sterile inflammation. Macrophages are a heterogeneous group of phagocytes of the innate immune system and serve as sentinels to detect loss of tissue integrity. Macrophages show a remarkable plasticity and undergo phenotypical changes in response to injury and repair. Under basal conditions, tissue-resident macrophages are distributed in various organ systems and have critical functions in tissue development and the maintenance of homeostasis. Inflammatory conditions, such as major trauma, lead to the rapid recruitment of blood-derived monocytes that mature into macrophages as well as direct recruitment of macrophages from the cavity that surrounds the injured organ. This leads to augmentation of the pool of tissue-resident macrophages. Besides their essential role in sensing tissue damage and initiating inflammation, macrophages contribution critically to tissue repair and wound healing, ultimately allowing full restoration. Dysregulated sterile inflammation and defective healing result in chronic inflammatory disease with persistent tissue damage. In this review, we summarize the cellular and molecular mechanisms that lead to activation of sterile inflammation, recruitment of immune cells and initiation of wound healing. We focus on the pivotal role of macrophages played in this context.

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Acknowledgements

We would like to thank Servier for providing Servier Medical Art, which was used for the creation of figures. M.P. is supported by the German Research Foundation (DFG) with a Research Fellowship (PE 2737/1–1). P.K. is supported by grants from the Canadian Institute of Health Research (CIHR), Alberta Innovates Health Solutions (AIHS), the Heart and Stroke Foundation of Canada and the Canada Research Chairs programme.

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  1. Department of Pharmacology and Physiology, University of Calgary, Calgary, AB, Canada

    Moritz Peiseler & Paul Kubes

  2. Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

    Moritz Peiseler & Paul Kubes

  3. I. Department of Medicine, University Medical Centre Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany

    Moritz Peiseler

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This work is in compliance with all ethical standards. All procedures involving animal research were approved by the University of Calgary Animal Care Committee and were in compliance with Canadian Council for Animal Care Guidelines.

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Peiseler, M., Kubes, P. Macrophages play an essential role in trauma-induced sterile inflammation and tissue repair. Eur J Trauma Emerg Surg 44, 335–349 (2018). https://doi.org/10.1007/s00068-018-0956-1

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