Anti eotaxin-2 antibodies attenuate the initiation and progression of experimental atherosclerosis

Mor, Adi; Afek, Arnon; Entin–Meer, Michal; Keren, Gad; George, Jacob

doi:10.4236/wjcd.2013.34054

Cited by 8 publications

(9 citation statements)

References 26 publications

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“…CM-101 is a humanised monoclonal antibody (mAb) that targets the human chemokine CCL24. Previous studies have shown that administration of CM-101, by binding CCL24 with high affinity, reduced proinflammatory responses in animal models of several diseases including atherosclerosis, rheumatoid arthritis and multiple sclerosis 29–31. This experimental evidence supports the ability of CM-101 to significantly interfere with proinflammatory processes in vivo.…”

Section: Introductionsupporting

confidence: 71%

Blockade of CCL24 with a monoclonal antibody ameliorates experimental dermal and pulmonary fibrosis

Mor

Segal-Salto²,

Katav

et al. 2019

Annals of the Rheumatic Diseases

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ObjectivesWe aimed to assess the expression of the CCL24 chemokine in systemic sclerosis (SSc) and to evaluate the possible pathogenic implications of the CCL24/CCR3 axis using both in vitro and in vivo models. We further investigated the efficacy of an anti-CCL24 monoclonal antibody (mAb), CM-101, in inhibiting cell activation as well as dermal and pulmonary inflammation and fibrosis in experimental animal models.MethodsWe used ELISA and fluorescence immunohistochemistry to determine CCL24 levels in serum and CCL24/CCR3 expression in skin biopsies of SSc patients. Skin fibroblasts and endothelial cells treated with CCL24 or SSc serum with or without CM-101 were used to follow cell activation and differentiation. Prevention and treatment in vivo bleomycin (BLM)-induced models were used to evaluate experimental dermal and pulmonary fibrosis progression following treatment with the CM-101 mAb.ResultsCCL24 circulating levels were significantly elevated in SSc patients. CCL24/CCR3 expression was strongly increased in SSc skin. Blockade of CCL24 with CM-101 significantly reduced the activation of dermal fibroblasts and their transition to myofibroblasts induced by SSc serum. CM-101 was also able to significantly inhibit endothelial cell activation induced by CCL24. In BLM-induced experimental animal models, CM-101 profoundly inhibited both dermal and pulmonary fibrosis and inflammation.ConclusionsCCL24 plays an important role in pathological processes of skin and lung inflammation and fibrosis. Inhibition of CCL24 by CM-101 mAb can be potentially beneficial for therapeutic use in SSc patients.

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Section: Introductionsupporting

confidence: 71%

Blockade of CCL24 with a monoclonal antibody ameliorates experimental dermal and pulmonary fibrosis

Mor

Segal-Salto²,

Katav

et al. 2019

Annals of the Rheumatic Diseases

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“…The anti-inflammatory and antifibrotic properties of blocking CCL24 in models of atherosclerosis, systemic sclerosis and idiopathic pulmonary fibrosis were previously shown. [30][31][32]42 In this publication we demonstrate that CCL24 also plays a significant role in liver fibrosis primarily by influencing fibroblasts. These results imply that CCL24 influences fibroblast activation in a dual pathway, primarily by acting directly on fibroblast activation through the CCR3 receptor, but also via an augmented inflammatory response.…”

Section: Discussionmentioning

confidence: 66%

“…Furthermore, we demonstrated that treatment with an anti-CCL24 monoclonal antibody reduced both the inflammatory and fibrotic pathways in preclinical models of systemic sclerosis. This anti-inflammatory activity of CCL24 blocking monoclonal antibody was also shown in multiple inflammatory preclinical models, including models of atherosclerosis, 30 rheumatoid arthritis 31 and encephalomyelitis. 32 In the current study, we assessed the potential involvement of the CCL24-CCR3 axis in liver inflammation and fibrosis associated with NAFLD/NASH.…”

Section: Inflammation Fibrosis Steatosismentioning

confidence: 67%

A blocking monoclonal antibody to CCL24 alleviates liver fibrosis and inflammation in experimental models of liver damage

Segal-Salto¹,

Barashi²,

Katav³

et al. 2020

JHEP Reports

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Correspondence adimor@chemomab.com (A. Mor). Graphical abstract CCL24 CCR3 Immune cells C M -1 0 1 C M -1 0 1Highlights CCL24 is a chemokine that regulates inflammatory and fibrotic activities through its receptor, CCR3.Significant expression of CCL24 and CCR3 were found in liver biopsies and blood samples from patients with NAFLD/NASH. CM-101, a monoclonal antibody that selectively targets CCL24, significantly attenuates fibrotic and inflammatory processes.Blocking CCL24 may have a potential therapeutic effect in NASH and liver fibrosis. Lay summaryCCL24 is a chemokine that regulates inflammation and fibrosis. It was found to be significantly expressed in patients with non-alcoholic steatohepatitis, in whom it regulates profibrotic processes in the liver. Herein, we show that blockade of CCL24 using a monoclonal antibody robustly attenuated liver fibrosis and inflammation in animal models, thus suggesting a potential therapeutic role for an anti-CCL24 agent.Background & Aims: C-C motif chemokine ligand 24 (CCL24) is a chemokine that regulates inflammatory and fibrotic activities through its receptor, C-C motif chemokine receptor (CCR3). The aim of the study was to evaluate the involvement of the CCL24-CCR3 axis in liver fibrosis and inflammation and to assess the potential of its blockade, by a monoclonal anti-CCL24 antibody, as a therapeutic strategy for non-alcoholic steatohepatitis (NASH) and liver fibrosis. Methods: Expression of CCL24 and CCR3 was evaluated in liver biopsies and blood samples. CCL24 involvement in NAFLD/ NASH pathogenesis was assessed in Ccl24 knockout mouse using the methionine-choline deficient (MCD) diet experimental model. Antifibrotic and anti-inflammatory effects of CM-101 were tested in the MCD and STAM mouse models and in the thioacetamide (TAA) model in rats. Liver enzymes, liver morphology, histology and collagen deposition, as well as fibrosisand inflammation-related protein expression were assessed. Activation of hepatic stellate cells (HSCs) was evaluated in the human LX2 cell line.Results: Patients with NASH and advanced NAFLD exhibited significant expression of both CCL24 and CCR3 in liver and blood samples. In the experimental MCD-diet model, Ccl24 knockout mice showed an attenuated liver damage response compared to wild-type mice, exhibiting reduced histological NAFLD activity scores and fibrosis, as well as lower levels of liver enzymes. Blocking CCL24 using CM-101 robustly reduced liver damage in 3 experimental animal models (MCD, STAM and TAA), as demonstrated by attenuation of liver fibrosis and NAFLD activity score. Furthermore, blocking CCL24 by CM-101 significantly inhibited CCL24-induced HSC motility, a-SMA expression and pro-collagen I secretion.Conclusion: Our results reveal that blocking CCL24 significantly attenuates liver fibrosis and inflammation and may have a potential therapeutic effect in patients with NASH and/or liver fibrosis.

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“…In a study using ApoE knockout (KO) mice, administration of anti-eotaxin-2 polyclonal blocking antibodies was shown to reduce early atheroma. When administered continuously, it promoted stabilisation of atheroma ( Mor et al 2013 ). These findings suggest the possibility that eosinophil chemoattractive proteins, which can be delivered either by inflammatory cells or by parasitic elements, are involved in the physiopathology of atherogenesis.…”

Section: Discussionmentioning

confidence: 99%

Characterisation of the vascular pathology in Sigmodon hispidus (Rodentia: Cricetidae) following experimental infection with Angiostrongylus costaricensis (Nematoda: Metastrongylidae)

Vasconcelos

Mota

Pelajo-Machado

2017

Mem. Inst. Oswaldo Cruz

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BACKGROUNDAngiostrongylus costaricensis is a nematode that causes human abdominal angiostrongyliasis, a disease found mainly in Latin American countries and particularly in Brazil and Costa Rica. Its life cycle involves exploitation of both invertebrate and vertebrate hosts. Its natural reservoir is a vertebrate host, the cotton rat Sigmodon hispidus. The adult worms live in the ileo-colic branches of the upper mesenteric artery of S. hispidus, causing periarteritis. However, there is a lack of data on the development of vasculitis in the course of infection.OBJECTIVE To describe the histopathology of vascular lesions in S. hispidus following infection with A. costaricensis.METHODS Twenty-one S. hispidus were euthanised at 30, 50, 90 and 114 days post-infection (dpi), and guts and mesentery (including the cecal artery) were collected. Tissues were fixed in Carson’s Millonig formalin, histologically processed for paraffin embedding, sectioned with a rotary microtome, and stained with hematoxylin-eosin, resorcin-fuchsin, Perls, Sirius Red (pH = 10.2), Congo Red, and Azan trichrome for brightfield microscopy analysis.FINDINGS At 30 and 50 dpi, live eggs and larvae were present inside the vasa vasorum of the cecal artery, leading to eosinophil infiltrates throughout the vessel adventitia and promoting centripetal vasculitis with disruption of the elastic layers. Disease severity increased at 90 and 114 dpi, when many worms had died and the intensity of the vascular lesions was greatest, with intimal alterations, thrombus formation, iron accumulation, and atherosclerosis.CONCLUSION In addition to abdominal angiostrongyliasis, our data suggest that this model could be very useful for autoimune vasculitis and atherosclerosis studies.

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Anti eotaxin-2 antibodies attenuate the initiation and progression of experimental atherosclerosis

Cited by 8 publications

References 26 publications

Blockade of CCL24 with a monoclonal antibody ameliorates experimental dermal and pulmonary fibrosis

Blockade of CCL24 with a monoclonal antibody ameliorates experimental dermal and pulmonary fibrosis

A blocking monoclonal antibody to CCL24 alleviates liver fibrosis and inflammation in experimental models of liver damage

Characterisation of the vascular pathology in Sigmodon hispidus (Rodentia: Cricetidae) following experimental infection with Angiostrongylus costaricensis (Nematoda: Metastrongylidae)

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