Skip to main content
Top
Published in: European Journal of Trauma and Emergency Surgery 3/2018

01-06-2018 | Review Article

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

Authors: Moritz Peiseler, Paul Kubes

Published in: European Journal of Trauma and Emergency Surgery | Issue 3/2018

Login to get access

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.
Literature
1.
go back to reference WHO. Injuries and Violence: the facts. Geneva: World Health Organization. 2014. WHO. Injuries and Violence: the facts. Geneva: World Health Organization. 2014.
7.
go back to reference Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992;101(6):1644–55.PubMedCrossRef Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992;101(6):1644–55.PubMedCrossRef
8.
go back to reference Angele MK, Faist E. Clinical review: immunodepression in the surgical patient and increased susceptibility to infection. Crit Care (London England). 2002;6(4):298–305.CrossRef Angele MK, Faist E. Clinical review: immunodepression in the surgical patient and increased susceptibility to infection. Crit Care (London England). 2002;6(4):298–305.CrossRef
11.
go back to reference Geissmann F, Jung S, Littman DR. Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity. 2003;19(1):71–82.PubMedCrossRef Geissmann F, Jung S, Littman DR. Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity. 2003;19(1):71–82.PubMedCrossRef
37.
go back to reference Mills CD. M1 and M2 macrophages: oracles of health and disease. Critical reviews in immunology. 2012;32(6):463–88.PubMedCrossRef Mills CD. M1 and M2 macrophages: oracles of health and disease. Critical reviews in immunology. 2012;32(6):463–88.PubMedCrossRef
43.
go back to reference Witmer-Pack MD, Hughes DA, Schuler G, Lawson L, McWilliam A, Inaba K, et al. Identification of macrophages and dendritic cells in the osteopetrotic (op/op) mouse. J Cell Sci. 1993;104(Pt 4):1021–9.PubMed Witmer-Pack MD, Hughes DA, Schuler G, Lawson L, McWilliam A, Inaba K, et al. Identification of macrophages and dendritic cells in the osteopetrotic (op/op) mouse. J Cell Sci. 1993;104(Pt 4):1021–9.PubMed
58.
go back to reference Quintana FJ, Cohen IR. Heat shock proteins as endogenous adjuvants in sterile and septic inflammation. J Immunol. 2005;175(5):2777–82.PubMedCrossRef Quintana FJ, Cohen IR. Heat shock proteins as endogenous adjuvants in sterile and septic inflammation. J Immunol. 2005;175(5):2777–82.PubMedCrossRef
69.
go back to reference Tsung A, Hoffman RA, Izuishi K, Critchlow ND, Nakao A, Chan MH, et al. Hepatic ischemia/reperfusion injury involves functional TLR4 signaling in nonparenchymal cells. J Immunol. 2005;175(11):7661–8.PubMedCrossRef Tsung A, Hoffman RA, Izuishi K, Critchlow ND, Nakao A, Chan MH, et al. Hepatic ischemia/reperfusion injury involves functional TLR4 signaling in nonparenchymal cells. J Immunol. 2005;175(11):7661–8.PubMedCrossRef
80.
go back to reference DeMaria EJ, Pellicane JV, Lee RB. Hemorrhagic shock in endotoxin-resistant mice: improved survival unrelated to deficient production of tumor necrosis factor. J Trauma. 1993;35(5):720–4 (discussion 4–5).PubMedCrossRef DeMaria EJ, Pellicane JV, Lee RB. Hemorrhagic shock in endotoxin-resistant mice: improved survival unrelated to deficient production of tumor necrosis factor. J Trauma. 1993;35(5):720–4 (discussion 4–5).PubMedCrossRef
81.
go back to reference Gill R, Ruan X, Menzel CL, Namkoong S, Loughran P, Hackam DJ, et al. Systemic inflammation and liver injury following hemorrhagic shock and peripheral tissue trauma involve functional TLR9 signaling on bone marrow-derived cells and parenchymal cells. Shock (Augusta Ga). 2011;35(2):164–70. https://doi.org/10.1097/SHK.0b013e3181eddcab.CrossRef Gill R, Ruan X, Menzel CL, Namkoong S, Loughran P, Hackam DJ, et al. Systemic inflammation and liver injury following hemorrhagic shock and peripheral tissue trauma involve functional TLR9 signaling on bone marrow-derived cells and parenchymal cells. Shock (Augusta Ga). 2011;35(2):164–70. https://​doi.​org/​10.​1097/​SHK.​0b013e3181eddcab​.CrossRef
92.
go back to reference Peiser L, Mukhopadhyay S, Gordon S. Scavenger receptors in innate immunity. Curr Opin Immunol. 2002;14(1):123–8.PubMedCrossRef Peiser L, Mukhopadhyay S, Gordon S. Scavenger receptors in innate immunity. Curr Opin Immunol. 2002;14(1):123–8.PubMedCrossRef
94.
go back to reference DiPietro LA. Wound healing: the role of the macrophage and other immune cells. Shock (Augusta Ga). 1995;4(4):233–40.CrossRef DiPietro LA. Wound healing: the role of the macrophage and other immune cells. Shock (Augusta Ga). 1995;4(4):233–40.CrossRef
96.
go back to reference Berse B, Brown LF, Van de Water L, Dvorak HF, Senger DR. Vascular permeability factor (vascular endothelial growth factor) gene is expressed differentially in normal tissues, macrophages, and tumors. Mol Biol Cell. 1992;3(2):211 – 20.PubMedPubMedCentralCrossRef Berse B, Brown LF, Van de Water L, Dvorak HF, Senger DR. Vascular permeability factor (vascular endothelial growth factor) gene is expressed differentially in normal tissues, macrophages, and tumors. Mol Biol Cell. 1992;3(2):211 – 20.PubMedPubMedCentralCrossRef
97.
99.
go back to reference Rappolee DA, Mark D, Banda MJ, Werb Z. Wound macrophages express TGF-alpha and other growth factors in vivo: analysis by mRNA phenotyping. Science (New York, NY). 1988;241(4866):708–12.CrossRef Rappolee DA, Mark D, Banda MJ, Werb Z. Wound macrophages express TGF-alpha and other growth factors in vivo: analysis by mRNA phenotyping. Science (New York, NY). 1988;241(4866):708–12.CrossRef
100.
go back to reference Shimokado K, Raines EW, Madtes DK, Barrett TB, Benditt EP, Ross R. A significant part of macrophage-derived growth factor consists of at least two forms of PDGF. Cell. 1985;43(1):277–86.PubMedCrossRef Shimokado K, Raines EW, Madtes DK, Barrett TB, Benditt EP, Ross R. A significant part of macrophage-derived growth factor consists of at least two forms of PDGF. Cell. 1985;43(1):277–86.PubMedCrossRef
131.
go back to reference Browder W, Williams D, Pretus H, Olivero G, Enrichens F, Mao P, et al. Beneficial effect of enhanced macrophage function in the trauma patient. Annals of surgery. 1990;211(5):605 – 12 (discussion 12–3).PubMedPubMedCentral Browder W, Williams D, Pretus H, Olivero G, Enrichens F, Mao P, et al. Beneficial effect of enhanced macrophage function in the trauma patient. Annals of surgery. 1990;211(5):605 – 12 (discussion 12–3).PubMedPubMedCentral
140.
go back to reference Lam SW, Leenen LP, van Solinge WW, Hietbrink F, Huisman A. Comparison between the prognostic value of the white blood cell differential count and morphological parameters of neutrophils and lymphocytes in severely injured patients for 7-day in-hospital mortality. Biomark: Biochem Indicat Exposure, Response, Suscept Chem. 2012;17(7):642–7. https://doi.org/10.3109/1354750x.2012.712161.CrossRef Lam SW, Leenen LP, van Solinge WW, Hietbrink F, Huisman A. Comparison between the prognostic value of the white blood cell differential count and morphological parameters of neutrophils and lymphocytes in severely injured patients for 7-day in-hospital mortality. Biomark: Biochem Indicat Exposure, Response, Suscept Chem. 2012;17(7):642–7. https://​doi.​org/​10.​3109/​1354750x.​2012.​712161.CrossRef
Metadata
Title
Macrophages play an essential role in trauma-induced sterile inflammation and tissue repair
Authors
Moritz Peiseler
Paul Kubes
Publication date
01-06-2018
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Trauma and Emergency Surgery / Issue 3/2018
Print ISSN: 1863-9933
Electronic ISSN: 1863-9941
DOI
https://doi.org/10.1007/s00068-018-0956-1

Other articles of this Issue 3/2018

European Journal of Trauma and Emergency Surgery 3/2018 Go to the issue