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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

CCR2 Expression in Neutrophils Plays a Critical Role in Their Migration Into the Joints in Rheumatoid Arthritis

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Author(s):
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Talbot, Jhimmy [1] ; Bianchini, Francine J. [1] ; Nascimento, Danilele C. [1] ; Oliveira, Rene D. R. [1] ; Souto, Fabricio O. [1] ; Pinto, Larissa G. [1] ; Peres, Raphael S. [1] ; Silva, Jaqueline R. [1] ; Almeida, Sergio C. L. [1] ; Louzada-Junior, Paulo [1] ; Cunha, Thiago M. [1] ; Cunha, Fernando Q. [1] ; Alves-Filho, Jose C. [1]
Total Authors: 13
Affiliation:
[1] Univ Sao Paulo, Ribeirao Preto Med Sch, BR-14049900 Ribeirao Preto, SP - Brazil
Total Affiliations: 1
Document type: Journal article
Source: ARTHRITIS & RHEUMATOLOGY; v. 67, n. 7, p. 1751-1759, JUL 2015.
Web of Science Citations: 36
Abstract

ObjectiveInfiltration of neutrophils into the joints plays an important role in bone erosion and articular destruction in rheumatoid arthritis (RA). Neutrophil trafficking during inflammation is a process that involves activation of chemotactic receptors. Recent findings suggest that changes in chemotactic receptor patterns could occur in neutrophils under certain inflammatory conditions. The aim of this study was to evaluate the gain of responsiveness of neutrophils to CCL2 in RA patients and to assess the role of CCL2 in driving neutrophil infiltration into the joints. MethodsNeutrophils were purified from the peripheral blood of patients with RA or from mice with antigen-induced arthritis (AIA). Expression of CCR2 was evaluated using polymerase chain reaction, flow cytometry, and immunofluorescence analyses. In vitro chemotaxis to CCL2 was assayed to evaluate the functional significance of de novo CCR2 expression. The murine AIA model was used to evaluate the in vivo role of CCR2 in neutrophil infiltration into the joints. ResultsHigh CCR2 expression and responsiveness to CCL2 were observed in neutrophils from the blood of patients with early RA and in neutrophils from the blood and bone marrow of mice with AIA. Genetic deficiency or pharmacologic inhibition of CCR2 protected against the infiltration of neutrophils into the joints. This protection was not associated with an impairment of the neutrophil chemotactic ability or CXC chemokine production in the joints. Moreover, adoptive transfer of wild-type mouse neutrophils to CCR2-deficient mice restored neutrophil infiltration and the articular mechanical hyperalgesia associated with joint inflammation. ConclusionThese findings suggest that CCR2 is directly involved in the detrimental infiltration of neutrophils into the joints in patients with RA, showing a new inflammatory role of CCR2 during RA flares or active disease. (AU)

FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
Grantee:Fernando de Queiroz Cunha
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 11/19670-0 - Mechanisms involved in the pathophysiology of rheumatoid arthritis, pain and sepsis
Grantee:Fernando de Queiroz Cunha
Support type: Research Projects - Thematic Grants