Complement, natural antibodies, autoantibodies and tissue injury

Fleming, Sherry D.; Tsokos, George C.

doi:10.1016/j.autrev.2005.09.006

Cited by 73 publications

(71 citation statements)

References 23 publications

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“…Natural antibodies are endogenous, circulating antibodies of IgG and IgM isotypes that are poly-reactive (26). Natural antibodies efficiently activate complement, acting to clear apoptotic debris and as a first line of defense against pathogens (26). In situations of sterile inflammation such as ischemia/reperfusion injury, natural IgM and complement can bind self-antigens and initiate pathologic damage (27).…”

Section: Discussionmentioning

confidence: 99%

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Activation of innate and humoral immunity in the peripheral nervous system of ALS transgenic mice

Chiu

Phatnani

Kuligowski

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

176

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During injury to the nervous system, innate immune cells mediate phagocytosis of debris, cytokine production, and axon regeneration. In the neuro-degenerative disease amyotrophic lateral sclerosis (ALS), innate immune cells in the CNS are activated. However, the role of innate immunity in the peripheral nervous system (PNS) has not been well defined. In this study, we characterized robust activation of CD169/CD68/Iba1؉ macrophages throughout the PNS in mutant SOD1 G93A and SOD1 G37R transgenic mouse models of ALS. Macrophage activation occurred pre-symptomatically, and expanded from focal arrays within nerve bundles to a tissue-wide distribution following symptom onset. We found a striking dichotomy for immune cells within the spinal cord and PNS. Flow cytometry and GFP bone marrow chimeras showed that spinal cord microglia were mainly tissue resident derived, dendritic-like cells, whereas in peripheral nerves, the majority of activated macrophages infiltrated from the circulation. Humoral antibodies and complement localized to PNS tissue in tandem with macrophage recruitment, and deficiency in complement C4 led to decreased macrophage activation. Therefore, cross-talk between nervous and immune systems occurs throughout the PNS during ALS disease progression. These data reveal a progressive innate and humoral immune response in peripheral nerves that is separate and distinct from spinal cord immune activation in ALS transgenic mice.innate immunity ͉ macrophage ͉ peripheral nervous system ͉ neuroimmunology ͉ amyotrophic lateral sclerosis

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Activation of innate and humoral immunity in the peripheral nervous system of ALS transgenic mice

Chiu

Phatnani

Kuligowski

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

176

View full text Add to dashboard Cite

show abstract

“…The complement system is a key step in innate immunity, however, an overwhelming activation of complement can lead to severe tissue injury (1). Complement has been shown to be involved in diverse processes, such as angiogenesis, inflammation, tissue injury, and tissue regeneration (33).…”

Section: Discussionmentioning

confidence: 99%

“…uring diverse clinical procedures, transient ischemia/ reperfusion (IR) inflicts on organs or tissues and causes intense inflammation, both locally and systemically (1,2), which in turn leads to various injuries or even multiple organ failure that contributes to high mortality. Acute lung injury (ALI) is a common outcome of IR, which usually happens in intestinal ischemia and leads to a higher mortality of 60-80% (3).…”

mentioning

confidence: 99%

Endoplasmic Reticulum Stress of Neutrophils Is Required for Ischemia/Reperfusion–Induced Acute Lung Injury

Chen

Jia

et al. 2015

The Journal of Immunology

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Diverse clinical factors, including intestinal ischemia, contribute to acute lung injury (ALI), which has up to a 40% mortality rate. During the development of lung injury an immune response is elicited that exacerbates the lung insult. Neutrophils have been well studied in mediating the pulmonary insults through an assortment of mechanisms, such as release of granule contents and production of proinflammatory cytokines due to the overactivation of complement and cytokines. In this study, we found that enhanced endoplasmic reticulum (ER) stress was observed in infiltrated neutrophils in the early stage of an ALI mice model. In neutrophils, complement 5a (C5a) inspires strong ER stress through inositol-requiring kinase 1a and, to a less extent, the protein kinase R–like ER kinase signaling pathway. The granule release induced by C5a was ER stress mediated. Knowkdown of X-box–binding protein 1, a downstream signaling molecule of inositol-requiring kinase 1a, impaired granule release, based on myeloperoxidase production. Further analysis revealed that C5a induced ER stress by binding to C5a receptor in neutrophils. Using xbpf/f MRP8-cre mice in which X-box–binding protein 1 is deficient specifically in neutrophils and ER stress is deprived, we confirmed that ER stress in neutrophils was required for granule release in vivo and led to ALI, whereas dampening ER stress in neutrophils substantially alleviated ALI. Taken together, our results demonstrated that C5a receptor–mediated ER stress induced granule release in neutrophils, contributing to the development of ALI. This novel mechanism suggests a new potential therapeutic target in autophagy regulation for ALI.

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“…It is believed that both the innate and adaptive immune systems have an important role in I/R injury (4)(5)(6). Previous studies focused on the role of innate immune response such as reactive oxygen species, cytokines and chemokines, the complement system, and neutrophils (4,7).…”

mentioning

confidence: 99%

Treatment with Recombinant Trichinella spiralis Cathepsin B–like Protein Ameliorates Intestinal Ischemia/Reperfusion Injury in Mice by Promoting a Switch from M1 to M2 Macrophages

Liu

Wen

Zhan

et al. 2015

The Journal of Immunology

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Intestinal ischemia/reperfusion (I/R) injury, in which macrophages play a key role, can cause high morbidity and mortality. The switch from classically (M1) to alternatively (M2) activated macrophages, which is dependent on the activation of STAT6 signaling, has been shown to protect organs from I/R injuries. In the current study, the effects of recombinant Trichinella spiralis cathepsin B–like protein (rTsCPB) on intestinal I/R injury and the potential mechanism related to macrophage phenotypes switch were investigated. In a mouse I/R model undergoing 60-min intestinal ischemia followed by 2-h or 7-d reperfusion, we demonstrated that intestinal I/R caused significant intestinal injury and induced a switch from M2 to M1 macrophages, evidenced by a decrease in levels of M2 markers (arginase-1 and found in inflammatory zone protein), an increase in levels of M1 markers (inducible NO synthase and CCR7), and a decrease in the ratio of M2/M1 macrophages. RTsCPB reversed intestinal I/R-induced M2–M1 transition and promoted M1-M2 phenotype switch evidenced by a significant decrease in M1 markers, an increase in M2 markers, and the ratio of M2/M1 macrophages. Meanwhile, rTsCPB significantly ameliorated intestinal injury and improved intestinal function and survival rate of animals, accompanied by a decrease in neutrophil infiltration and an increase in cell proliferation in the intestine. However, a selective STAT6 inhibitor, AS1517499, reversed the protective effects of rTsCPB by inhibiting M1 to M2 transition. These findings suggest that intestinal I/R injury causes a switch from M2 to M1 macrophages and that rTsCPB ameliorates intestinal injury by promoting STAT6-dependent M1 to M2 transition.

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Complement, natural antibodies, autoantibodies and tissue injury

Cited by 73 publications

References 23 publications

Activation of innate and humoral immunity in the peripheral nervous system of ALS transgenic mice

Activation of innate and humoral immunity in the peripheral nervous system of ALS transgenic mice

Endoplasmic Reticulum Stress of Neutrophils Is Required for Ischemia/Reperfusion–Induced Acute Lung Injury

Treatment with Recombinant Trichinella spiralis Cathepsin B–like Protein Ameliorates Intestinal Ischemia/Reperfusion Injury in Mice by Promoting a Switch from M1 to M2 Macrophages

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