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Ca2+ released from calcium alginate gels can promote inflammatory responses in vitro and in vivo

机译:海藻酸钙凝胶释放的Ca2 +可以在体内和体外促进炎症反应

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In general, alginate hydrogels are considered to be biologically inert and are commonly used for biomedical purposes that require minimum inflammation. However, Ca2+, which is commonly used to crosslink alginate, is a critical second messenger in immune cell signaling, and little has been done to understand its effect on immune cell fate when delivered as a component of alginate gels. We found that dendritic cells (DCs) encapsulated in Ca 2+-crosslinked alginate (calcium alginate) secreted at least fivefold more of the inflammatory cytokine IL-1β when compared to DCs encapsulated in agarose and collagen gels, as well as DCs plated on tissue-culture polystyrene (TCPS). Plating cells on TCPS with the alginate polymer could not reproduce these results, whereas culturing DCs on TCPS with increasing concentrations of Ca2+ increased IL-1β, MHC class II and CD86 expression in a dose-dependent manner. In agreement with these findings, calcium alginate gels induced greater maturation of encapsulated DCs compared to barium alginate gels. When injected subcutaneously in mice, calcium alginate gels significantly upregulated IL-1β secretion from surrounding tissue relative to barium alginate gels, and similarly, the inflammatory effects of LPS were enhanced when it was delivered from calcium alginate gels rather than barium alginate gels. These results confirm that the Ca2+ used to crosslink alginate gels can be immunostimulatory and suggest that it is important to take into account Ca2+'s bioactive effects on all exposed cells (both immune and non-immune) when using calcium alginate gels for biomedical purposes. This work may strongly impact the way people use alginate gels in the future as well as provide insights into past work utilizing alginate gels.
机译:通常,藻酸盐水凝胶被认为是生物学惰性的,并且通常用于需要最少炎症的生物医学目的。然而,通常用于交联藻酸盐的Ca2 +是免疫细胞信号传导中的关键第二信使,而当以藻酸盐凝胶的形式递送时,对于了解其对免疫细胞命运的影响却鲜有做过。我们发现封装在Ca 2+交联的藻酸盐(藻酸钙)中的树突状细胞(DC)与琼脂糖和胶原凝胶封装的DC以及铺在组织上的DC相比,分泌的炎症细胞因子IL-1β至少多出五倍-培养聚苯乙烯(TCPS)。用藻酸盐聚合物在TCPS上电镀细胞不能重现这些结果,而在TCPS上培养浓度较高的Ca2 +的DC以剂量依赖性方式增加IL-1β,II类MHC和CD86表达。与这些发现一致的是,与藻酸钡凝胶相比,藻酸钙凝胶诱导了封装DC的更大的成熟度。当皮下注射给小鼠时,海藻酸钙凝胶相对于海藻酸钡凝胶显着上调了周围组织的IL-1β分泌,类似地,当从海藻酸钙凝胶而不是海藻酸钡凝胶中递送时,LPS的炎症作用增强。这些结果证实,用于藻酸盐凝胶交联的Ca2 +可以具有免疫刺激性,并建议在将藻酸盐钙凝胶用于生物医学目的时,考虑到Ca2 +对所有暴露细胞(免疫细胞和非免疫细胞)的生物活性非常重要。这项工作可能会极大地影响人们将来使用藻酸盐凝胶的方式,并提供有关使用藻酸盐凝胶的以往工作的见解。

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