Integrin-directed modulation of macrophage responses to biomaterials.
Integrin-directed modulation of macrophage responses to biomaterials.
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DOI：
10.1016/j.biomaterials.2014.01.007
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发表时间：
2014-04
期刊：
影响因子：
14
通讯作者：
Keselowsky, Benjamin G.
中科院分区：
文献类型：
--
作者：
Zaveri, Toral D.;Lewis, Jamal S.;Dolgova, Natalia V.;Clare-Salzler, Michael J.;Keselowsky, Benjamin G.
在材料为颗粒或块状形式的情况下，巨噬细胞是对植入生物材料的慢性炎症反应的主要介质。慢性炎症限制了许多植入医疗器械的性能和功能寿命，调节巨噬细胞与生物材料的相互作用以减轻这种反应将是有益的。细胞表面受体的整合素家族通过与非特异性吸附在生物材料表面上的粘附蛋白结合来介导细胞粘附。在这项工作中，整合素Mac-1（αMβ2）和RGD结合整合素的作用进行了研究，使用模型系统的颗粒和散装生物材料。具体地，研究了巨噬细胞响应于模型颗粒材料聚苯乙烯微粒的吞噬作用和炎性细胞因子分泌的功能。调理蛋白调节微粒摄取，整合素Mac-1和RGD结合整合素被发现以调理素依赖的方式控制微粒摄取。吸附的内毒素的存在并不影响微粒的摄取水平，但需要响应于微粒的炎性细胞因子的生产。此外，已证明整联蛋白Mac-1和结合RGD的整联蛋白影响对散装生物材料（皮下植入的聚对苯二甲酸乙二醇酯）的体内异物反应。当整合素Mac-1不存在时（约30%稀释）或当通过控制释放封闭肽（约45%稀释）阻断结合RGD的整合素时，形成较薄的异物包膜。这些发现表明整合素Mac-1和RGD结合整合素参与，并可作为治疗靶点，以减轻巨噬细胞对颗粒和散装生物材料的炎症反应。
Macrophages are the primary mediator of chronic inflammatory responses to implanted biomaterials, in cases when the material is either in particulate or bulk form. Chronic inflammation limits the performance and functional life of numerous implanted medical devices, and modulating macrophage interactions with biomaterials to mitigate this response would be beneficial. The integrin family of cell surface receptors mediates cell adhesion through binding to adhesive proteins nonspecifically adsorbed onto biomaterial surfaces. In this work, the roles of integrin Mac-1 (αMβ2) and RGD-binding integrins were investigated using model systems for both particulate and bulk biomaterials. Specifically, the macrophage functions of phagocytosis and inflammatory cytokine secretion in response to a model particulate material, polystyrene microparticles were investigated. Opsonizing proteins modulated microparticle uptake, and integrin Mac-1 and RGD-binding integrins were found to control microparticle uptake in an opsonin-dependent manner. The presence of adsorbed endotoxin did not affect microparticle uptake levels, but was required for the production of inflammatory cytokines in response to microparticles. Furthermore, it was demonstrated that integrin Mac-1 and RGD-binding integrins influence the in vivo foreign body response to a bulk biomaterial, subcutaneously implanted polyethylene terephthalate. A thinner foreign body capsule was formed when integrin Mac-1 was absent (~30% thinner) or when RGD-binding integrins were blocked by controlled release of a blocking peptide (~45% thinner). These findings indicate integrin Mac-1 and RGD-binding integrins are involved and may serve as therapeutic targets to mitigate macrophage inflammatory responses to both particulate and bulk biomaterials.
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影响因子：
9.7
作者：
Acharya, Abhinav P.;Dolgova, Natalia V.;Keselowsky, Benjamin G.
通讯作者：
Keselowsky, Benjamin G.
DOI：
10.1007/s10029-004-0281-y
发表时间：
2005-03-01
期刊：
Hernia : the journal of hernias and abdominal wall surgery
影响因子：
--
作者：
Bracco, P;Brunella, V;Botto-Micca, F
通讯作者：
Botto-Micca, F
影响因子：
14
作者：
Acharya, Abhinav P.;Dolgova, Natalia V.;Keselowsky, Benjamin G.
通讯作者：
Keselowsky, Benjamin G.
影响因子：
4.8
作者：
FISHER, JE;CAULFIELD, MP;ROSENBLATT, M
通讯作者：
ROSENBLATT, M
影响因子：
2.2
作者：
Cunnick, Jess;Kaur, Pavinder;Heisterkamp, Nora
通讯作者：
Heisterkamp, Nora