Neutrophil FcγRIIA promotes IgG-mediated glomerular neutrophil capture via Abl/Src kinases

Nishi, Hiroshi; Furuhashi, Kazuhiro; Culleré, Xavier; Saggu, Gurpanna; Miller, Mark J.; Chen, Yunfeng; Rosetti, Florencia; Hamilton, Samantha; Yang, Lihua; Pittman, Spencer P.; Liao, Jiexi; Herter, Jan M.; Berry, Jeffrey C.; DeAngelo, Daniel J.; Zhu, Cheng; Tsokos, George C.; Mayadas, Tanya N.

doi:10.1172/jci94039

Cited by 50 publications

(41 citation statements)

References 72 publications

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“…21,32 Although c-Abl kinase is best known for it´s role in human leukemias, 20,33 accumulating data suggest that c-Abl exerts more pluripotent functions in different inflammatory conditions, such as endotoxemic lung damage, Ig-mediated renal injury, and nephrotoxicity. 25,26,34 In the present study, we could demonstrate that targeting c-Abl kinase with a specific inhibitor (GZD824) reduced c-Abl phosphorylation in both circulating neutrophils and in the pancreas of animals with AP. In order to define the contribution of neutrophils to the c-Abl kinase activity in the inflamed pancreas, animals were depleted of neutrophils.…”

Section: Discussionsupporting

confidence: 51%

“…It is widely accepted that c‐Abl kinase is a critical signaling molecule regulating cellular actin dynamics and cytoskeletal rearrangement . Although c‐Abl kinase is best known for it´s role in human leukemias, accumulating data suggest that c‐Abl exerts more pluripotent functions in different inflammatory conditions, such as endotoxemic lung damage, Ig‐mediated renal injury, and nephrotoxicity . In the present study, we could demonstrate that targeting c‐Abl kinase with a specific inhibitor (GZD824) reduced c‐Abl phosphorylation in both circulating neutrophils and in the pancreas of animals with AP.…”

Section: Discussionmentioning

confidence: 46%

“…Moreover, inhibition of c‐Abl kinase activity has been reported to reduce endotoxin‐induced neutrophilia and tissue damage in the lung . In addition, it has been showed that c‐Abl kinase is involved in vascular leakage formation in sepsis and in IgG‐mediated glomerular injury . Thus, accumulating evidence suggest that c‐Abl plays an important function in versatile inflammatory conditions but the potential role of c‐Abl kinase in the induction of severe AP is unknown.…”

Section: Introductionmentioning

confidence: 99%

“…24 In addition, it has been showed that c-Abl kinase is involved in vascular leakage formation in sepsis 25 and in IgG-mediated glomerular injury. 26 Thus, accumulating evidence suggest that c-Abl plays an important function in versatile inflammatory conditions but the potential role of c-Abl kinase in the induction of severe AP is unknown. In this context, it is interesting to note that c-Abl kinase has been suggested to regulate ROS generation in neutrophils 27 and ROS has been shown to be involved in the expulsion of NETs from neutrophils.…”

Section: Introductionmentioning

confidence: 99%

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c-Abl kinase regulates neutrophil extracellular trap formation, inflammation, and tissue damage in severe acute pancreatitis

Madhi

Rahman

Mörgelin³

et al. 2019

Journal of Leukocyte Biology

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Neutrophil extracellular traps (NETs) are involved in acute pancreatitis (AP) but mechanisms controlling NET expulsion in AP are incompletely understood. Herein, we examined the role of c‐Abelson (c‐Abl) kinase in NET formation and tissue damage in severe AP. AP was induced by taurocholate infusion into pancreatic duct or intraperitoneal administration of l‐arginine in mice. Pancreatic, lung, and blood samples were collected and levels of phosphorylated c‐Abl kinase, citrullinated histone 3, DNA‐histone complexes, myeloperoxidase, amylase, cytokines, and CXC chemokines were quantified. Citrullinated histone 3, reactive oxygen species (ROS), and NET formation were determined in bone marrow neutrophils. Taurocholate challenge increased phosphorylation of c‐Abl kinase and levels of citrullinated histone 3 in the pancreas as well as DNA‐histone complexes in the plasma. Administration of the c‐Abl kinase inhibitor GZD824 not only abolished activation of c‐Abl kinase but also decreased levels of citrullinated histone 3 in the pancreas and DNA‐histone complexes in the plasma of animals with AP. Moreover, GZD824 decreased plasma levels of amylase, IL‐6, and MMP‐9 as well as edema, acinar cell necrosis, hemorrhage, CXC chemokine formation, and neutrophil infiltration in the inflamed pancreas. A beneficial effect of c‐Abl kinase inhibition was confirmed in l‐arginine‐induced pancreatitis. In vitro, inhibition of c‐Abl kinase reduced TNF‐α‐induced formation of ROS, histone 3 citrullination, and NETs in isolated bone marrow neutrophils. Our findings demonstrate that c‐Abl kinase regulates NET formation in the inflamed pancreas. In addition, inhibition of c‐Abl kinase reduced pancreatic tissue inflammation, and damage in AP. Thus, targeting c‐Abl kinase might be a useful way to protect the pancreas in severe AP.

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Section: Discussionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 46%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

c-Abl kinase regulates neutrophil extracellular trap formation, inflammation, and tissue damage in severe acute pancreatitis

Madhi

Rahman

Mörgelin³

et al. 2019

Journal of Leukocyte Biology

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“…However, such technique may be limited to studies of acute inflammatory disease. [50][51][52] Because of the short lifespan of donor neutrophils (within 24 hours), 53 daily adoptive transfer of neutrophils to study chronic diseases can be technically challenging in addition to causing unnecessary stress to the subjects that may artificially complicate data interpretation. Therefore, neutrophil-selective IL6-deficiency may be required to test a role of neutrophil IL6 in AAA, a hypothesis that merits further investigation.…”

Section: Discussionmentioning

confidence: 99%

Deficiency of immunoglobulin E protects mice from experimental abdominal aortic aneurysms

Deng

Zhang

et al. 2020

FASEB j.

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Allergic asthma with high plasma IgE levels is a significant risk factor of human abdominal aortic aneurysm (AAA). This study tests a direct role of IgE in angiotensin‐II (Ang‐II) perfusion‐ and peri‐aortic CaCl2 injury‐induced AAA in mice. In both models, IgE‐deficiency in Apoe−/−Ige−/− mice blunts AAA growth and reduces lesion accumulation of macrophages, CD4+ and CD8+ T cells, and lesion MHC class‐II expression, CD31+ microvessel growth, and media smooth muscle cell loss, compared with those from Apoe−/− control mice. Real time‐PCR reveals significant reductions in expression of neutrophil chemoattractants MIP‐2α and CXCL5 in AAA lesions or macrophages from Apoe−/−Ige−/− mice, along with reduced lesion Ly6G+ neutrophil accumulation. Consistent with reduced lesion inflammatory cell accumulation, we find significant reductions of plasma and AAA lesion IL6 expression in Apoe−/−Ige−/− mice. Immunofluorescent staining and FACS analysis show that AAA lesion neutrophils express FcεR1. Mechanistic study demonstrates that IgE induces neutrophil FcεR1 expression, activates MAPK signaling, and promotes IL6 production. This study supports a direct role of IgE in AAA by promoting lesion chemokine expression, inflammatory cell accumulation, MAPK signaling, and cytokine expression. IgE inhibition may represent a novel therapeutic approach in AAA management.

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Parietal epithelial cell dysfunction in crescentic glomerulonephritis

et al. 2021

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Crescentic glomerulonephritis represents a group of kidney diseases characterized by rapid loss of kidney function and the formation of glomerular crescents. While the role of the immune system has been extensively studied in relation to the development of crescents, recent findings show that parietal epithelial cells play a key role in the pathophysiology of crescent formation, even in the absence of immune modulation. This review highlights our current understanding of parietal epithelial cell biology and the reported physiological and pathological roles that these cells play in glomerular lesion formation, especially in the context of crescentic glomerulonephritis.

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Neutrophil FcγRIIA promotes IgG-mediated glomerular neutrophil capture via Abl/Src kinases

Cited by 50 publications

References 72 publications

c-Abl kinase regulates neutrophil extracellular trap formation, inflammation, and tissue damage in severe acute pancreatitis

c-Abl kinase regulates neutrophil extracellular trap formation, inflammation, and tissue damage in severe acute pancreatitis

Deficiency of immunoglobulin E protects mice from experimental abdominal aortic aneurysms

Parietal epithelial cell dysfunction in crescentic glomerulonephritis

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