Skeletal muscle reperfusion injury is mediated by  neutrophils and the complement membrane attack complex

Kyriakides, Constantinos; Austen, William G.; Wang, Yong; Favuzza, Joanne; Kobzik, Lester; Moore, Francis D.; Hechtman, Herbert B.

doi:10.1152/ajpcell.1999.277.6.c1263

Cited by 75 publications

(46 citation statements)

References 32 publications

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“…Given this underlying rationale, it was our expectation that Ig deficiency would attenuate classic pathway activation of complement and thus limit IRI in the kidney. In addition to preventing complement activation through the classic pathway, the absence of IgG would similarly eliminate potential interactions with Fc receptors on infiltrating leukocytes, the presence of which is key in IRI (13,36). Surprisingly, our results unequivocally show that renal IRI proceeds independently from Ig, as RAG-1(Ϫ/Ϫ) mice were equally susceptible to IRI as wildtype controls.…”

Section: Discussionmentioning

confidence: 58%

Injury in renal ischemia-reperfusion is independent from immunoglobulins and T lymphocytes

Park

Haas

Cunningham

et al. 2002

American Journal of Physiology-Renal Physiology

120

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Ischemia-reperfusion injury (IRI) is a complex and incompletely understood process involving a cascade of events that culminates in apoptotic and/or necrotic cell death. Natural IgM antibodies and complement have been implicated in the pathogenesis of IRI in a variety of organ systems as have T lymphocytes in renal IRI. To investigate the role of Ig and T lymphocytes in renal IRI, recombination-activating gene (RAG)-1-deficient mice were studied. RAG-1(−/−) mice were not protected from acute renal failure induced by 27.5 min of bilateral renal ischemia and subsequent reperfusion [serum urea nitrogen levels 30 h after reperfusion, 155.2 ± 5.6 and 152.8 ± 11.4 mg/dl in RAG-1(−/−) and wild-type mice, respectively; n = 13 each]. Histological examination showed acute tubular necrosis and neutrophilic infiltration with no significant differences between groups. In contrast with other organ systems, Igs were not found in kidneys at time points ranging from 1 min to 30 h after ischemia. Thus Igs and mature T lymphocytes do not appear to play a significant role in the pathogenesis of IRI in the kidney.

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Section: Discussionmentioning

confidence: 58%

Injury in renal ischemia-reperfusion is independent from immunoglobulins and T lymphocytes

Park

Haas

Cunningham

et al. 2002

American Journal of Physiology-Renal Physiology

120

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“…44 The complement system seems to be a major contributor to the tissue damage that occurs after ischemia and reperfusion. Complement activation following ischemia/ reperfusion occurs during myocardial infarction 45,46 ; ischemia of the intestine, 47 hind limb, 48 and kidney 49 ; hemorrhagic shock 50 ; sepsis 51 ; and pulmonary injury. 52 As yet there is no definitive answer to the question of how complement is activated after I/R.…”

Section: I/r Injurymentioning

confidence: 99%

The Role of Complement in Inflammatory Diseases From Behind the Scenes into the Spotlight

Markiewski

Lambris

2007

The American Journal of Pathology

599

575

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Our understanding of the biology of the complement system has undergone a drastic metamorphosis since its original discovery. This system, which was traditionally primarily described as a "complement" to humoral immunity, is now perceived as a central constituent of innate immunity, defending the host against pathogens, coordinating various events during inflammation, and bridging innate and adaptive immune responses. Complement is an assembly of proteins found in the blood and body fluids and on cell surfaces. Soluble complement components form the proteolytic cascade, whose activation leads to the generation of complement effectors that target various cells involved in the immune response. Membrane-bound receptors and regulators transmit signals from complement effectors to target cells and limit complement activation to the surfaces of pathogens and damaged or activated host cells. The multiple interconnections among complement proteins, immune cells, and mediators provide an excellent mechanism to protect the organism against infections and support the repair of damaged tissues. However, disturbances in this "defense machinery" contribute to the pathogenesis of various diseases. The role of complement in various inflammatory disorders is multifaceted; for example, the activation of complement can significantly contribute to inflammation-mediated tissue damage, whereas inherited or acquired complement deficiencies highly favor the development of autoimmunity.

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“…Endothelium damaged by hypoxic stress activates complement, leading to elevated vascular permeability, release of anaphylatoxins and the accumulation of neutrophils (98). Experimental studies indicated complement activation after ischemia/reperfusion in several organs, including lung, liver, gut, kidney, myocardium and skeletal muscle (99)(100)(101)(102)(103)(104)(105).…”

Section: Ischemia/reperfusion Injuries and Cardiovascular Diseasesmentioning

confidence: 99%

New Insights of an Old Defense System: Structure, Function, and Clinical Relevance of the Complement System

Ehrnthaller

Ignatius

Gebhard

et al. 2010

Mol Med

190

154

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The complement system was discovered a century ago as a potent defense cascade of innate immunity. After its first description, continuous experimental and clinical research was performed, and three canonical pathways of activation were established. Upon activation by traumatic or surgical tissue damage, complement reveals beneficial functions of pathogen and danger defense by sensing and clearing injured cells. However, the latest research efforts have provided a more distinct insight into the complement system and its clinical subsequences. Complement has been shown to play a significant role in the pathogenesis of various inflammatory processes such as sepsis, multiorgan dysfunction, ischemia/reperfusion, cardiovascular diseases and many others. The three well-known activation pathways of the complement system have been challenged by newer findings that demonstrate direct production of central complement effectors (for example, C5a) by serine proteases of the coagulation cascade. In particular, thrombin is capable of producing C5a, which not only plays a decisive role on pathogens and infected/damaged tissues, but also acts systemically. In the case of uncontrolled complement activation, "friendly fire" is generated, resulting in the destruction of healthy host tissue. Therefore, the traditional research that focuses on a mainly positive-acting cascade has now shifted to the negative effects and how tissue damage originated by the activation of the complement can be contained. In a translational approach including structure-function relations of this ancient defense system, this review provides new insights of complement-mediated clinical relevant diseases and the development of complement modulation strategies and current research aspects.

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Skeletal muscle reperfusion injury is mediated by neutrophils and the complement membrane attack complex

Cited by 75 publications

References 32 publications

Injury in renal ischemia-reperfusion is independent from immunoglobulins and T lymphocytes

Injury in renal ischemia-reperfusion is independent from immunoglobulins and T lymphocytes

The Role of Complement in Inflammatory Diseases From Behind the Scenes into the Spotlight

New Insights of an Old Defense System: Structure, Function, and Clinical Relevance of the Complement System

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