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

Nan Hu; Johanna Westra; Abraham Rutgers; Berber Doornbos-Van der Meer; Minke G Huitema; Coen A Stegeman; Wayel H Abdulahad; Simon C Satchell; Peter W Mathieson; Peter Heeringa; Cees G M Kallenberg

doi:10.1186/ar3534

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

Nan Hu, Johanna Westra, Abraham Rutgers, Berber Doornbos-Van der Meer, Minke G Huitema, Coen A Stegeman, Wayel H Abdulahad, Simon C Satchell, Peter W Mathieson, Peter Heeringa, Cees G M Kallenberg

Research output: Contribution to journal › Article (Academic Journal) › peer-review

34 Citations (Scopus)

Abstract

INTRODUCTION: 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.

Translated title of the contribution	Decreased CXCR1 and CXCR2 expression on neutrophils in anti-neutrophil cytoplasmic autoantibody-associated vasculitides potentially increases neutrophil adhesion and impairs migration
Original language	English
Pages (from-to)	R201
Number of pages	1
Journal	Arthritis Research and Therapy
Volume	13
Issue number	6
DOIs	https://doi.org/10.1186/ar3534
Publication status	Published - Dec 2011

Keywords

Adult
Aged
Aged, 80 and over
Antibodies, Antineutrophil Cytoplasmic
Cell Adhesion
Cell Line
Cell Membrane
Cell Movement
Cells, Cultured
Dose-Response Relationship, Drug
Enzyme-Linked Immunosorbent Assay
Female
Flow Cytometry
Humans
Interleukin-8
Male
Middle Aged
Neutrophils
Receptors, Interleukin-8A
Receptors, Interleukin-8B
Tumor Necrosis Factor-alpha
Vasculitis

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Mathieson, P. W.
1/11/08 → 1/05/12
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Hu, N., Westra, J., Rutgers, A., Doornbos-Van der Meer, B., Huitema, M. G., Stegeman, C. A., Abdulahad, W. H., Satchell, S. C., Mathieson, P. W., Heeringa, P., & Kallenberg, C. G. M. (2011). Decreased CXCR1 and CXCR2 expression on neutrophils in anti-neutrophil cytoplasmic autoantibody-associated vasculitides potentially increases neutrophil adhesion and impairs migration. Arthritis Research and Therapy, 13(6), R201. https://doi.org/10.1186/ar3534

@article{c5f8bc611a7e41ffbc0f13a4eec7339b,

title = "Decreased CXCR1 and CXCR2 expression on neutrophils in anti-neutrophil cytoplasmic autoantibody-associated vasculitides potentially increases neutrophil adhesion and impairs migration",

abstract = "INTRODUCTION: 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.",

keywords = "Adult, Aged, Aged, 80 and over, Antibodies, Antineutrophil Cytoplasmic, Cell Adhesion, Cell Line, Cell Membrane, Cell Movement, Cells, Cultured, Dose-Response Relationship, Drug, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Humans, Interleukin-8, Male, Middle Aged, Neutrophils, Receptors, Interleukin-8A, Receptors, Interleukin-8B, Tumor Necrosis Factor-alpha, Vasculitis",

author = "Nan Hu and Johanna Westra and Abraham Rutgers and {Doornbos-Van der Meer}, Berber and Huitema, {Minke G} and Stegeman, {Coen A} and Abdulahad, {Wayel H} and Satchell, {Simon C} and Mathieson, {Peter W} and Peter Heeringa and Kallenberg, {Cees G M}",

year = "2011",

month = dec,

doi = "10.1186/ar3534",

language = "English",

volume = "13",

pages = "R201",

journal = "Arthritis Research and Therapy",

issn = "1478-6354",

publisher = "BioMed Central",

number = "6",

}

Hu, N, Westra, J, Rutgers, A, Doornbos-Van der Meer, B, Huitema, MG, Stegeman, CA, Abdulahad, WH, Satchell, SC, Mathieson, PW, Heeringa, P & Kallenberg, CGM 2011, 'Decreased CXCR1 and CXCR2 expression on neutrophils in anti-neutrophil cytoplasmic autoantibody-associated vasculitides potentially increases neutrophil adhesion and impairs migration', Arthritis Research and Therapy, vol. 13, no. 6, pp. R201. https://doi.org/10.1186/ar3534

Decreased CXCR1 and CXCR2 expression on neutrophils in anti-neutrophil cytoplasmic autoantibody-associated vasculitides potentially increases neutrophil adhesion and impairs migration. / Hu, Nan; Westra, Johanna; Rutgers, Abraham et al.
In: Arthritis Research and Therapy, Vol. 13, No. 6, 12.2011, p. R201.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

TY - JOUR

T1 - Decreased CXCR1 and CXCR2 expression on neutrophils in anti-neutrophil cytoplasmic autoantibody-associated vasculitides potentially increases neutrophil adhesion and impairs migration

AU - Hu, Nan

AU - Westra, Johanna

AU - Rutgers, Abraham

AU - Doornbos-Van der Meer, Berber

AU - Huitema, Minke G

AU - Stegeman, Coen A

AU - Abdulahad, Wayel H

AU - Satchell, Simon C

AU - Mathieson, Peter W

AU - Heeringa, Peter

AU - Kallenberg, Cees G M

PY - 2011/12

Y1 - 2011/12

N2 - INTRODUCTION: 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.

AB - INTRODUCTION: 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antibodies, Antineutrophil Cytoplasmic

KW - Cell Adhesion

KW - Cell Line

KW - Cell Membrane

KW - Cell Movement

KW - Cells, Cultured

KW - Dose-Response Relationship, Drug

KW - Enzyme-Linked Immunosorbent Assay

KW - Female

KW - Flow Cytometry

KW - Humans

KW - Interleukin-8

KW - Male

KW - Middle Aged

KW - Neutrophils

KW - Receptors, Interleukin-8A

KW - Receptors, Interleukin-8B

KW - Tumor Necrosis Factor-alpha

KW - Vasculitis

U2 - 10.1186/ar3534

DO - 10.1186/ar3534

M3 - Article (Academic Journal)

C2 - 22152684

SN - 1478-6354

VL - 13

SP - R201

JO - Arthritis Research and Therapy

JF - Arthritis Research and Therapy

IS - 6

ER -

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

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