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Article: Decreased CXCR1 and CXCR2 expression on neutrophils in anti-neutrophil cytoplasmic autoantibody-associated vasculitides potentially increases neutrophil adhesion and impairs migration

TitleDecreased CXCR1 and CXCR2 expression on neutrophils in anti-neutrophil cytoplasmic autoantibody-associated vasculitides potentially increases neutrophil adhesion and impairs migration
Authors
Issue Date2011
Citation
Arthritis Research and Therapy, 2011, v. 13 n. 6 How to Cite?
AbstractIntroduction: In anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV), persistent inflammation within the vessel wall suggests perturbed neutrophil trafficking leading to accumulation of activated neutrophils in the microvascular compartment. CXCR1 and CXCR2, being major chemokine receptors on neutrophils, are largely responsible for neutrophil recruitment. We speculate that down-regulated expression of CXCR1/2 retains neutrophils within the vessel wall and, consequently, leads to vessel damage.Methods: Membrane expression of CXCR1/2 on neutrophils was assessed by flow cytometry. Serum levels of interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-α), angiopoietin 1 and angiopoietin 2 from quiescent and active AAV patients and healthy controls (HC) were quantified by ELISA. Adhesion and transendothelial migration of isolated neutrophils were analyzed using adhesion assays and Transwell systems, respectively.Results: Expression of CXCR1 and CXCR2 on neutrophils was significantly decreased in AAV patients compared to HC. Levels of IL-8, which, as TNFα, dose-dependently down-regulated CXCR1 and CXCR2 expression on neutrophils in vitro, were significantly increased in the serum of patients with active AAV and correlated negatively with CXCR1/CXCR2 expression on neutrophils, even in quiescent patients. Blocking CXCR1 and CXCR2 with repertaxin increased neutrophil adhesion and inhibited migration through a glomerular endothelial cell layer.Conclusions: Expression of CXCR1 and CXCR2 is decreased in AAV, potentially induced by circulating proinflammatory cytokines such as IL-8. Down-regulation of these chemokine receptors could increase neutrophil adhesion and impair its migration through the glomerular endothelium, contributing to neutrophil accumulation and, in concert with ANCA, persistent inflammation within the vessel wall. © 2012 Hu et al.; licensee BioMed Central Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/195504
ISSN
2015 Impact Factor: 3.979
2015 SCImago Journal Rankings: 1.617
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorHu, N-
dc.contributor.authorWestra, J-
dc.contributor.authorRutgers, A-
dc.contributor.authorDoornbos-Van der Meer, B-
dc.contributor.authorHuitema, MG-
dc.contributor.authorStegeman, CA-
dc.contributor.authorAbdulahad, WH-
dc.contributor.authorSatchell, SC-
dc.contributor.authorMathieson, PW-
dc.contributor.authorHeeringa, P-
dc.contributor.authorM Kallenberg, CG-
dc.date.accessioned2014-02-28T06:12:15Z-
dc.date.available2014-02-28T06:12:15Z-
dc.date.issued2011-
dc.identifier.citationArthritis Research and Therapy, 2011, v. 13 n. 6-
dc.identifier.issn1478-6354-
dc.identifier.urihttp://hdl.handle.net/10722/195504-
dc.description.abstractIntroduction: In anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV), persistent inflammation within the vessel wall suggests perturbed neutrophil trafficking leading to accumulation of activated neutrophils in the microvascular compartment. CXCR1 and CXCR2, being major chemokine receptors on neutrophils, are largely responsible for neutrophil recruitment. We speculate that down-regulated expression of CXCR1/2 retains neutrophils within the vessel wall and, consequently, leads to vessel damage.Methods: Membrane expression of CXCR1/2 on neutrophils was assessed by flow cytometry. Serum levels of interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-α), angiopoietin 1 and angiopoietin 2 from quiescent and active AAV patients and healthy controls (HC) were quantified by ELISA. Adhesion and transendothelial migration of isolated neutrophils were analyzed using adhesion assays and Transwell systems, respectively.Results: Expression of CXCR1 and CXCR2 on neutrophils was significantly decreased in AAV patients compared to HC. Levels of IL-8, which, as TNFα, dose-dependently down-regulated CXCR1 and CXCR2 expression on neutrophils in vitro, were significantly increased in the serum of patients with active AAV and correlated negatively with CXCR1/CXCR2 expression on neutrophils, even in quiescent patients. Blocking CXCR1 and CXCR2 with repertaxin increased neutrophil adhesion and inhibited migration through a glomerular endothelial cell layer.Conclusions: Expression of CXCR1 and CXCR2 is decreased in AAV, potentially induced by circulating proinflammatory cytokines such as IL-8. Down-regulation of these chemokine receptors could increase neutrophil adhesion and impair its migration through the glomerular endothelium, contributing to neutrophil accumulation and, in concert with ANCA, persistent inflammation within the vessel wall. © 2012 Hu et al.; licensee BioMed Central Ltd.-
dc.languageeng-
dc.relation.ispartofArthritis Research and Therapy-
dc.titleDecreased CXCR1 and CXCR2 expression on neutrophils in anti-neutrophil cytoplasmic autoantibody-associated vasculitides potentially increases neutrophil adhesion and impairs migration-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1186/ar3534-
dc.identifier.pmid22152684-
dc.identifier.scopuseid_2-s2.0-82955246727-
dc.identifier.volume13-
dc.identifier.issue6-
dc.identifier.isiWOS:000301175700021-

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