Damage-Associated Molecular Patterns and the Systemic Immune Consequences of Severe Thermal Injury

Sepsis is a life-threatening clinical syndrome and one of the most challenging health problems in the world. Pathologically, sepsis and septic shock are caused by a dysregulated host immune response to infection, which can eventually lead to multiple organ failure and even death. As an adaptor transporter between the endoplasmic reticulum and Golgi apparatus, stimulator of interferon response cGAMP interactor 1 (STING1, also known as STING or TMEM173) has been found to play a vital role at the intersection of innate immunity, inflammation, autophagy, and cell death in response to invading microbial pathogens or endogenous host damage. There is ample evidence that impaired STING1, through its immune and non-immune functions, is involved in the pathological process of sepsis. In this review, we discuss the regulation and function of the STING1 pathway in sepsis and highlight it as a suitable drug target for the treatment of lethal infection.

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“…PAMPs and DAMPs can activate various innate immune pathways and have become important therapeutic targets for sepsis. 7 , 8 , 9 …”

Section: Introductionmentioning

confidence: 99%

STING1 in sepsis: Mechanisms, functions, and implications

Zhang

Kang

Tang

2022

Chinese Journal of Traumatology

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“…This review refers to the adult population. For both burns and hemorrhagic shock following a major trauma, the ages of higher incidence are similar, between the 20 to 40 years, mainly males (the data refer to high income countries [1][2][3]). Burns are the fourth leading cause of traumatic events in the world.…”

Section: Introductionmentioning

confidence: 99%

“…Damage-associated molecular patterns (DAMPS) play a role in the pathophysiology of the post-injury systemic inflammatory response that begins immediately after injury [3,12,13]. This response is present in trauma, surgical, and critically ill patients, although in burns it has a peculiar and unique severity and magnitude [14,15].…”

Section: Introductionmentioning

confidence: 99%

“…DAMPs are expelled after tissue damage, and are immunologically active and clinically relevant [3]. Some DAMPs are intracellular proteins from different organelles that are released after cellular death (for example high mobility group box 1, HMGB1); others are non-protein (ATP, DNA), extracellular matrix, or cell membrane components secreted after host recognition of tissue damage [3]. When released in the extracellular environment, they are able for activating innate and adaptive immunity.…”

Section: Introductionmentioning

confidence: 99%

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The Role of DAMPS in Burns and Hemorrhagic Shock Immune Response: Pathophysiology and Clinical Issues. Review

Pantalone

Bergamini

Martellucci

et al. 2021

IJMS

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Severe or major burns induce a pathophysiological, immune, and inflammatory response that can persist for a long time and affect morbidity and mortality. Severe burns are followed by a “hypermetabolic response”, an inflammatory process that can be extensive and become uncontrolled, leading to a generalized catabolic state and delayed healing. Catabolism causes the upregulation of inflammatory cells and innate immune markers in various organs, which may lead to multiorgan failure and death. Burns activate immune cells and cytokine production regulated by damage-associated molecular patterns (DAMPs). Trauma has similar injury-related immune responses, whereby DAMPs are massively released in musculoskeletal injuries and elicit widespread systemic inflammation. Hemorrhagic shock is the main cause of death in trauma. It is hypovolemic, and the consequence of volume loss and the speed of blood loss manifest immediately after injury. In burns, the shock becomes evident within the first 24 h and is hypovolemic-distributive due to the severely compromised regulation of tissue perfusion and oxygen delivery caused by capillary leakage, whereby fluids shift from the intravascular to the interstitial space. In this review, we compare the pathophysiological responses to burns and trauma including their associated clinical patterns.

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“…Pain shock caused by burns causes changes in the endocrine organs, in particular the adrenal glands, which produce a wide range of hormones that control the nature of protective and compensatory processes and mechanisms of adaptation of the body after exposure to this exogenous factor [5,9,18,27,34]. Burns, as a stress factor, also cause circulatory and microcirculation disorders in the organs, which is manifested in plethora and vasodilation, edema, stasis and subsequent tissue hypoxia [7,16,28,32]. Endogenous intoxication of the body, the source of which is a burn wound, plays a significant role in the pathogenesis of burn injury [1,11,12,23,25].…”

Section: Introductionmentioning

confidence: 99%

Histological changes of the adrenal glands vessels after experimental thermal trauma and under the conditions of lyophilized xenoskin use

Kulbitska

2021

Biomed. and Biosoc. Anthrop.

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Burns, as a stress factor, cause circulatory and microcirculation disorders in the organs. In the scientific literature, the issues of structural reorganization of the vascular bed of the adrenal glands in thermal trauma and under conditions of correction by lyophilized xenoskin are insufficiently covered and therefore require further study. The aim of our study was to study the microscopic changes of the vessels of the adrenal glands in the dynamics after experimental thermal trauma and under conditions of correction. The experiment was performed on adult white male rats. Grade III burn (18-20 % of the skin surface) was applied under thiopental-sodium anesthesia with copper plates heated in water to a temperature of 97-1000C, on the epilated surface of the skin of the back for 10 seconds. One day after the thermal injury, an early necrectomy was performed and the wound was covered with a substrate of lyophilized xenoskin. Animal decapitation and microscopic changes were studied at days 7, 14, and 21 of injury modeling. The manufacture of histopreparations was carried out according to conventional methods. Histological examinations after experimental thermal trauma and correction of xenoskin substrate on the 7th day showed that already in this period of the experiment there were less pronounced destructive changes in the structure of the vessels of the adrenal glands. Some blood vessels were unevenly filled and dilated. The hemocapillaries of the microcirculatory tract are blood-filled, the vessel wall is destructively altered, and perivascular edema is present. On the 14th day of the experiment, moderately blood vessels were observed. The wall of large vessels is slightly swollen, partially thickened, hemocapillaries are moderately blood-filled, with dilated lumens and continuous endothelial lining. Under the conditions of application of the substrate of lyophilized xenoskin on the 21st day of the experiment, the structural organization of the vascular bed of the adrenal glands was significantly better compared to the previous terms of the study. Most vessels had evenly dilated lumens and moderate blood supply, and wall edema was insignificant. The walls of microvessels are preserved, well structured, endotheliocytes without severe damage, without signs of infiltration and edema. Thus, the results of microscopic examination showed that early necrectomy, and subsequent closure of the wound with a substrate of lyophilized xenoskin, creates optimal conditions for regenerative processes in both burns and vascular bed of the adrenal glands. On the 7th day after the burn and under conditions of correction, the study of the vascular bed of the adrenal glands showed a moderate degree of destructive changes in the vascular bed of the adrenal glands and the initial signs of their regeneration. In the late terms (14-21 days) of the experiment the relative normalization of cellular parenchymal components of the organ was established against the background of restoration of the structural organization of the microcirculatory tract.

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Damage-Associated Molecular Patterns and the Systemic Immune Consequences of Severe Thermal Injury

Cited by 37 publications

References 106 publications

STING1 in sepsis: Mechanisms, functions, and implications

STING1 in sepsis: Mechanisms, functions, and implications

The Role of DAMPS in Burns and Hemorrhagic Shock Immune Response: Pathophysiology and Clinical Issues. Review

Histological changes of the adrenal glands vessels after experimental thermal trauma and under the conditions of lyophilized xenoskin use

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