Mast cells mediate neutrophil recruitment during atherosclerotic plaque progression. Issue 2 (August 2015)

• Record Type: Journal Article
• Authors: Wezel, Anouk; Lagraauw, H. Maxime; van der Velden, Daniël; de Jager, Saskia C.A.; Quax, Paul H.A.; Kuiper, Johan; Bot, Ilze
• Is Part Of: Atherosclerosis. Volume 241:Issue 2(2015)
• Page Start: 289
• Page End: 296
• Publication Date: 2015-08
• Subjects: Atherosclerotic plaque development and progression -- Mast cells -- Neutrophils -- Recruitment -- Influx -- Chemokines; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2015.05.028
• Languages: English
• ISSNs: 0021-9150

Abstract

Abstract: Aims: Activated mast cells have been identified in the intima and perivascular tissue of human atherosclerotic plaques. As mast cells have been described to release a number of chemokines that mediate leukocyte fluxes, we propose that activated mast cells may play a pivotal role in leukocyte recruitment during atherosclerotic plaque progression. Methods and results: Systemic IgE-mediated mast cell activation in apoE −/− μMT mice resulted in an increase in atherosclerotic lesion size as compared to control mice, and interestingly, the number of neutrophils was highly increased in these lesions. In addition, peritoneal mast cell activation led to a massive neutrophil influx into the peritoneal cavity in C57Bl6 mice, whereas neutrophil numbers in mast cell deficient Kit(W -sh /W -sh ) mice were not affected. Within the newly recruited neutrophil population, increased levels of CXCR2 + and CXCR4 + neutrophils were observed after mast cell activation. Indeed, mast cells were seen to contain and release CXCL1 and CXCL12, the ligands for CXCR2 and CXCR4. Intriguingly, peritoneal mast cell activation in combination with anti-CXCR2 receptor antagonist resulted in decreased neutrophil recruitment, thus establishing a prominent role for the CXCL1/CXCR2 axis in mast cell-mediated neutrophil recruitment. Conclusions: Our data suggest that chemokines, and in particular CXCL1, released from activated mast cells induce neutrophil recruitment to the site of inflammation, thereby aggravating the ongoing inflammatory response and thus affecting plaque progression and destabilization. Highlights: Systemic mast cell activation increased atherosclerotic plaque development. Systemic mast cell activation induces neutrophil accumulation. Peritoneal mast cell activation caused an influx of CXCR2 + and CXCR4 + neutrophils. Mast cells express and secrete CXCL1 or CXCL12, the ligands for CXCR2 and CXCR4. CXCR2 inhibition significantly reduced mast cell-mediated neutrophil recruitment.