Induction of Biologically Active Antineutrophil Cytoplasmic Antibodies by Immunization with Human Apoptotic Polymorphonuclear Leukocytes

Rauova, Lubica; Gilburd, Boris; Zurgil, Naomi; Blank, Miri; Guegas, Larisa L.; Brickman, Chaim M.; Cebecauer, L; Deutsch, Mordechai; Wiik, Allan; Shoenfeld, Yehuda

doi:10.1006/clim.2002.5194

Cited by 28 publications

(16 citation statements)

References 26 publications

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“…45 Furthermore, PMN apoptosis is necessary to induce the production of autoantibody against PMNs. 46 It is possible that TRAIL and autoantibodies against PMNs may interdependently contribute to the pathogenesis of neutropenia in SLE, and additional experiments are necessary to clarify their relationship.…”

Section: Discussionmentioning

confidence: 99%

TNF-related apoptosis-inducing ligand is involved in neutropenia of systemic lupus erythematosus

Matsuyama

Yamamoto

Higashimoto

et al. 2004

Blood

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Neutropenia is a common laboratory finding in systemic lupus erythematosus (SLE). However, the molecular mechanism of SLE neutropenia has not been fully explained. In this study, we examined whether TNF-related apoptosisinducing ligand (TRAIL) is involved in the pathogenesis of SLE neutropenia using samples from SLE patients. Serum TRAIL levels in SLE patients with neutropenia were significantly higher than those of SLE patients without neutropenia and healthy volunteers. Serum TRAIL levels showed a significant negative correlation with neutrophil counts in SLE patients. The expression of TRAIL receptor 3 was significantly lower in SLE patients with neutropenia than in patients without neutropenia or in healthy volunteers. Treatment with glucocorticoids negated the decrease of TRAIL receptor 3 expression on neutrophils of SLE patients. TRAIL may accelerate neutrophil apoptosis of neutrophils from SLE patients, and autologous T cells of SLE patients, which express TRAIL on surface, may kill autologous neutrophils. IntroductionNeutropenia in systemic lupus erythematosus (SLE) was first described more than 70 years ago 1 and is found in about 50%-60% of patients with SLE. 2 Clinically, increased susceptibility to infections is a major cause of morbidity and mortality in patients with SLE. 3,4 In this regard, not only treatment with adrenal glucocorticoids and/or immunosuppressive drugs but also decreased numbers of polymorphonuclear neutrophils (PMNs) is obviously responsible for the increased incidence of infections. [5][6][7][8][9] However, the detailed molecular mechanism of neutropenia in SLE has not been fully elucidated.Traditionally, PMNs have been considered to be the first line cell component of the body defense mechanism against bacterial pathogens and were regarded as terminally differentiated cells incapable of protein synthesis and committed to death within 72 hours. [10][11][12] Recently, it was indicated that neutrophils were not only capable of receiving signals from different proinflammatory cytokines and chemokines, but also could synthesize many important proinflammatory cytokines and chemokines to modulate immune responses, such as interferon-gamma (IFN-␥), tumor necrosis factor alpha (TNF-␣), and interleukin-8 (IL-8). 13,14 And these proinflammatory mediators, relevant to the inflamed site in vivo, also act to modulate the constitutive death of neutrophils. 15,16 Regarding neutrophil apoptosis, Fas 17 and TNF-␣ 18 were reported to be able to shorten neutrophil lifespan at early time points. Recently, it was reported that TNF-related apoptosis-inducing ligand (TRAIL) could accelerate neutrophil apoptosis. 19 Also, TRAIL was reported to be involved in the monocyte apoptosis induced by T cells in SLE. 20 However, the role of TRAIL in neutropenia of SLE is still unclear.In this study, we have investigated the TRAIL receptors on neutrophils and TRAIL-induced neutrophil apoptosis using samples from SLE patients. A difference in the expression pattern of TRAIL receptors between SLE patients and healt...

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Section: Discussionmentioning

confidence: 99%

TNF-related apoptosis-inducing ligand is involved in neutropenia of systemic lupus erythematosus

Matsuyama

Yamamoto

Higashimoto

et al. 2004

Blood

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“…As a result, GSD1b patients experience severe neutropenia and are highly susceptible to recurrent bacterial infections, aphthous stomatitis, or inflammatory bowel disease [135]. Increased neutrophil death was also observed in autoimmune diseases such as anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis [136,137] and systemic lupus erythematosus (SLE) [138]. Interestingly, alteration of neutrophil death has also been recognized as one of the responses elicited by stress.…”

Section: Neutrophil Apoptosis In Inflammatory and Immunological Diseasesmentioning

confidence: 99%

Constitutive neutrophil apoptosis: Mechanisms and regulation

2007

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Neutrophil constitutive death is a critical cellular process for modulating neutrophil number and function, and it plays an essential role in neutrophil homeostasis and the resolution of inflammation. Neutrophils die due to programmed cell death or apoptosis. In this article, we review recent studies on the mechanism of neutrophil apoptosis. The involvement of caspase, calpain, reactive oxygen species, cellular survival/death signaling pathways, mitochondria, and BCL-2 family member proteins are discussed. The fate of neutrophils can be influenced within the inflammatory microenvironment. We summarize the current understanding regarding the modulation of neutrophil apoptotic death by various extracellular stimuli such as proinflammatory cytokines, cell adhesion, phagocytosis, red blood cells, and platelets. The involvement of neutrophil apoptosis in infectious and inflammatory diseases is also addressed. Am. J. Hematol. 83:288-295, 2008. V

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“…Apoptotic neutrophils increase their proteinase 3 (PR3) and myeloperoxidase (MPO) expression (4,6 -8). In fact, injection of either apoptotic human or rat neutrophils in mice and rats induces ANCA generation (9,10). These ANCA induced respiratory bursts in human neutrophils (9).…”

mentioning

confidence: 99%

“…In fact, injection of either apoptotic human or rat neutrophils in mice and rats induces ANCA generation (9,10). These ANCA induced respiratory bursts in human neutrophils (9). Moreover, ANCA can opsonize apoptotic neutrophils.…”

mentioning

confidence: 99%

Fever-Like Temperatures Affect Neutrophil NF-κB Signaling, Apoptosis, and ANCA-Antigen Expression

Kettritz¹,

Choi²,

Salanova³

et al. 2006

Journal of the American Society of Nephrology

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The neutrophil is pivotal to ANCA vasculitis pathogenesis. Fever frequently complicates ANCA diseases. This study investigated the effects of short-term heat exposure on apoptosis in neutrophils that were treated with LPS, GM-CSF, IL-8, and dexamethasone. All compounds delayed apoptosis. Heat abrogated the apoptosis-delaying effect of LPS without affecting constitutive apoptosis or delayed apoptosis by GM-CSF, IL-8, or dexamethasone. The heat effect was dose dependent over the 39 to 42°C range. NF-B but not extracellular signal-regulated kinase, p38 mitogen-activated protein kinase (MAPK), or phosphatidylinositol 3-kinase/Akt controlled LPS-delayed apoptosis. Furthermore, LPS-induced IB␣ degradation, DNA binding, and NF-B-dependent gene transcription activation were abrogated by short-term heat. When core temperatures were raised to 40.5°C for 30 min in mice, LPS-induced neutrophil NF-B activation also was prevented. Short-term heat removed heat-shock protein 90 from the IB kinase complex, resulting in failure of LPS-induced IB kinase activation. Despite delayed apoptosis, ANCA antigen expression was increased in LPS-treated neutrophils. ANCA antigen increase was prevented by p38 MAPK inhibition and by heat exposure. Heat exposure did not inhibit LPS-induced p38 MAPK phosphorylation. Instead, apoptosis-mediated p38 MAPK degradation was accelerated, thereby decreasing the p38 MAPK that was available for LPS-mediated ANCA antigen upregulation. These data suggest that fever-like temperatures modulate neutrophil behavior in this disease.

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Induction of Biologically Active Antineutrophil Cytoplasmic Antibodies by Immunization with Human Apoptotic Polymorphonuclear Leukocytes

Cited by 28 publications

References 26 publications

TNF-related apoptosis-inducing ligand is involved in neutropenia of systemic lupus erythematosus

TNF-related apoptosis-inducing ligand is involved in neutropenia of systemic lupus erythematosus

Constitutive neutrophil apoptosis: Mechanisms and regulation

Fever-Like Temperatures Affect Neutrophil NF-κB Signaling, Apoptosis, and ANCA-Antigen Expression

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