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CXCR2 is critical for bacterial control and development of joint damage and pain in Staphylococcus aureus-induced septic arthritis in mouse.

CXCR2 is critical for bacterial control and development of joint damage and pain in Staphylococcus aureus-induced septic arthritis in mouse.
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Boff D, Oliveira VLS, Queiroz Junior CM, Silva TA, Allegretti M, Verri WA, Proost P, Teixeira MM, Amaral FA,


Boff D, Oliveira VLS, Queiroz Junior CM, Silva TA, Allegretti M, Verri WA, Proost P, Teixeira MM, Amaral FA, (click to view)

Boff D, Oliveira VLS, Queiroz Junior CM, Silva TA, Allegretti M, Verri WA, Proost P, Teixeira MM, Amaral FA,

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European journal of immunology 2017 11 22() doi 10.1002/eji.201747198
Abstract

Staphylococcus aureus is the main pathogen associated with septic arthritis. Upon infection, neutrophils are quickly recruited to the joint by different chemoattractants, especially CXCR1/2 binding chemokines. Although their excessive accumulation is associated with intense pain and permanent articular damage, neutrophils have an important function in controlling bacterial burden. This work aimed to study the role of CXCR2 in the control of infection, hypernociception and tissue damage in S. aureus-induced septic arthritis in mice. The kinetics of neutrophil recruitment correlated with the bacterial load recovered from inflamed joint after intra-articular injection of S. aureus. Treatment of mice from the start of infection with the non-competitive antagonist of CXCR1/2, DF2156A, reduced neutrophil accumulation, cytokine production in the tissue, joint hypernociception and articular damage. However, early DF2156A treatment increased the bacterial load locally. CXCR2 was important for neutrophil activation and clearance of bacteria in vitro and in vivo. Start of treatment with DF2156A 3 days after infection prevented increase in bacterial load and reduced the hypernociception in the following days, but did not improve tissue damage. In conclusion, treatment with DF2156A seems be effective in controlling tissue inflammation and dysfunction but its effects are highly dependent on the timing of the treatment start. This article is protected by copyright. All rights reserved.

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