Deletion of the chemokine receptor CCR2 attenuates foreign body reaction to implants in mice

Castro, Pollyana Ribeiro; Marques, Suzane M.; Viana, Celso Tarso Rodrigues; Campos, Paula Peixoto; Ferreira, Mônica Alves Neves Diniz; Barcelos, Lucíola da Silva; Andrade, Sílvia Passos

doi:10.1016/j.mvr.2014.07.002

Cited by 16 publications

(9 citation statements)

References 39 publications

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“…Recently, the sensor literature underscored that the presence of MΦ at sites of sensor implantation reduces sensor performance including CGM (Klueh et al 2014a; Klueh et al 2014b; Novak and Reichert 2015; Novak et al 2014). Moreover, it is known that mice deficient in CCL2 (MCP-1) experience minimal fibrotic reactions in response to an implant (Castro et al 2014; Moore et al 2015; Skokos et al 2011). Recent studies suggested that this diminished fibrotic response is at least in part due to a compromised TNF and NFκB induction in these CCL2 deficient mice.…”

Section: Discussionmentioning

confidence: 99%

“…Alternatively, subcutaneous implantation studies showed that the recruitment and migration of macrophages in CCL2 KO mice is similar to WT mice (Kyriakides et al 2004), suggesting it is not a player in MΦ recruitment. Nevertheless it is known that CCL2 is a requirement in the formation of FBGC (Castro et al 2014). It must be stated that the phenotype and number of macrophages induced in response to an inflammatory signal are dependent on the type of injury, tissue site, implant and/or biomaterial, as well as the time point of the evaluation of the inflammatory response (e.g.…”

Section: Discussionmentioning

confidence: 99%

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Impact of CCL2 and CCR2 chemokine/receptor deficiencies on macrophage recruitment and continuous glucose monitoring in vivo

Klueh

Czajkowski

Ludzinska

et al. 2016

Biosensors and Bioelectronics

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The accumulation of macrophages (MΦ) at the sensor-tissue interface is thought to be a major player in controlling tissue reactions and sensor performance in vivo. Nevertheless until recently no direct demonstration of the causal relationship between MΦ aggregation and loss of sensor function existed. Using a Continuous Glucose Monitoring (CGM) murine model we previously demonstrated that genetic deficiencies of MΦ or depletion of MΦ decreased MΦ accumulation at sensor implantation sites, which led to significantly enhanced CGM performance, when compared to normal mice. Additional studies in our laboratories have also demonstrated that MΦ can act as “metabolic sinks” by depleting glucose levels at the implanted sensors in vitro and in vivo. In the present study we extended these observations by demonstrating that MΦ chemokine (CCL2) and receptor (CCR2) knockout mice displayed a decrease in inflammation and MΦ recruitment at sensor implantation sites, when compared to normal mice. This decreased MΦ recruitment significantly enhanced CGM performance when compared to control mice. These studies demonstrated the importance of the CCL2 family of chemokines and related receptors in MΦ recruitment and sensor performance and suggest chemokine targets for enhancing CGM in vivo.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Impact of CCL2 and CCR2 chemokine/receptor deficiencies on macrophage recruitment and continuous glucose monitoring in vivo

Klueh

Czajkowski

Ludzinska

et al. 2016

Biosensors and Bioelectronics

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“…In this model, the acellular and avascular synthetic matrix implanted subcutaneously in the dorsal of the animals induces the migration, proliferation and activation of various cells types responsible for the development of a fibrovascular tissue that underlies both acute and chronic pathological conditions (Almeida et al, 2014;Castro et al, 2012Castro et al, , 2014Marques et al, 2011). We report here that allopurinol exhibited both angiopreventive and angiopromoting effects on the fibrovascular tissue induced by synthetic matrix in mice.…”

Section: Introductionmentioning

confidence: 85%

Angiopreventive versus angiopromoting effects of allopurinol in the murine sponge model

Orellano

Almeida

Campos

et al. 2015

Microvascular Research

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“…For histology, based on our previous experience a minimum of n = 5/group (total n = 40 animals) was sufficient to give statistical significance in ANOVA tests when comparing treated groups with the control group. Furthermore, based on previous statistical analysis, we have established that counting 5 microscopic fields (8533 μm 2 per field) per treatment group was sufficient to maintain the standard deviation within a 10% variation 34 .…”

Section: Methodsmentioning

confidence: 99%

Low Concentration of Sodium Butyrate from Ultrabraid+NaBu suture, Promotes Angiogenesis and Tissue Remodelling in Tendon-bones Injury

Liu

Andrade

Castro

et al. 2016

Sci Rep

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Sodium butyrate (NaBu), a form of short-chain fatty acid (SCFA), acts classically as a potent anti-angiogenic agent in tumour angiogenesis models, some authors demonstrated that low concentrations of NaBu may contribute to healing of tendon-bone injury in part at least through promotion of tissue remodelling. Here, we investigated the effects of low-range concentrations of NaBu using in vitro and in vivo assays using angiogenesis as the primary outcome measure and the mechanisms through which it acts. We demonstrated that NaBu, alone or perfused from the UltraBraid+NaBu suture was pro-angiogenic at very low-range doses promoting migration, tube formation and cell invasion in bovine aortic endothelial cells (BAECs). Furthermore, cell exposure to low NaBu concentrations increased expression of proteins involved in angiogenic cell signalling, including p-PKCβ1, p-FAK, p-ERK1/2, p-NFκβ, p-PLCγ1 and p-VEGFR2. In addition, inhibitors of both VEGFR2 and PKCβ1 blocked the angiogenic response. In in vivo assays, low concentrations of NaBu induced neovascularization in sponge implants in mice, evidenced by increased numbers of vessels and haemoglobin content in these implants. The findings in this study indicate that low concentrations of NaBu could be an important compound to stimulate angiogenesis at a site where vasculature is deficient and healing is compromised.

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Deletion of the chemokine receptor CCR2 attenuates foreign body reaction to implants in mice

Cited by 16 publications

References 39 publications

Impact of CCL2 and CCR2 chemokine/receptor deficiencies on macrophage recruitment and continuous glucose monitoring in vivo

Impact of CCL2 and CCR2 chemokine/receptor deficiencies on macrophage recruitment and continuous glucose monitoring in vivo

Angiopreventive versus angiopromoting effects of allopurinol in the murine sponge model

Low Concentration of Sodium Butyrate from Ultrabraid+NaBu suture, Promotes Angiogenesis and Tissue Remodelling in Tendon-bones Injury

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