由I型胶原和高硫酸透明质酸组成的人工细胞外基质在无菌炎症条件下调节单核细胞向巨噬细胞的分化。

Biomatter Pub Date : 2012-10-01 DOI:10.4161/biom.22855
Jennifer Kajahn, Sandra Franz, Erik Rueckert, Inka Forstreuter, Vera Hintze, Stephanie Moeller, Jan C Simon
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引用次数: 83

摘要

巨噬细胞的非对抗激活常常干扰生物材料进入组织的整合。植入后,单核细胞从外周血被吸引到植入部位,在那里分化为巨噬细胞。来自植入生物材料周围无菌组织损伤的炎症信号通过自分泌和旁分泌机制介导单核细胞向炎性M1巨噬细胞(M1)的分化。抑制持续的M1分化被认为是促进种植体愈合的关键。在这里,我们探索由胶原和透明质酸(HA)或硫酸化HA衍生物组成的人工细胞外基质(aECM)是否调节这种单核细胞分化。我们使用含有MCP-1、IL-6和IFNγ的特异性细胞因子鸡尾酒模拟体外无菌组织损伤条件,诱导单核细胞产生与M1巨噬细胞相似的表型(CD71、HLA-DR高表达,但CD163不表达,释放大量促炎细胞因子IL-1β、IL-6、IL-8、IL-12和TNFα)。在含有高硫酸化HA的aecm存在时,单核细胞向M1的分化受到干扰。具体来说,促炎功能受损,表现为IL-1β、IL-8、IL-12和TNFα分泌减少。相反,诱导免疫调节细胞因子IL-10的释放和CD163的表达,这两种标志物都是抗炎M2巨噬细胞(M2)的特异性标志物。我们得出结论,由I型胶原和高硫酸化HA组成的aecm具有免疫调节能力,并将无菌损伤的促炎信号诱导的单核细胞向巨噬细胞分化向M2极化方向倾斜,表明它们是一种有效的生物材料涂层,可以改善其整合。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Artificial extracellular matrices composed of collagen I and high sulfated hyaluronan modulate monocyte to macrophage differentiation under conditions of sterile inflammation.

Artificial extracellular matrices composed of collagen I and high sulfated hyaluronan modulate monocyte to macrophage differentiation under conditions of sterile inflammation.

Artificial extracellular matrices composed of collagen I and high sulfated hyaluronan modulate monocyte to macrophage differentiation under conditions of sterile inflammation.

Artificial extracellular matrices composed of collagen I and high sulfated hyaluronan modulate monocyte to macrophage differentiation under conditions of sterile inflammation.

Integration of biomaterials into tissues is often disturbed by unopposed activation of macrophages. Immediately after implantation, monocytes are attracted from peripheral blood to the implantation site where they differentiate into macrophages. Inflammatory signals from the sterile tissue injury around the implanted biomaterial mediate the differentiation of monocytes into inflammatory M1 macrophages (M1) via autocrine and paracrine mechanisms. Suppression of sustained M1 differentiation is thought to be crucial to improve implant healing. Here, we explore whether artificial extracellular matrix (aECM) composed of collagen I and hyaluronan (HA) or sulfated HA-derivatives modulate this monocyte differentiation. We mimicked conditions of sterile tissue injury in vitro using a specific cytokine cocktail containing MCP-1, IL-6 and IFNγ, which induced in monocytes a phenotype similar to M1 macrophages (high expression of CD71, HLA-DR but no CD163 and release of high amounts of pro-inflammatory cytokines IL-1β, IL-6, IL-8, IL-12 and TNFα). In the presence of aECMs containing high sulfated HA this monocyte to M1 differentiation was disturbed. Specifically, pro-inflammatory functions were impaired as shown by reduced secretion of IL-1β, IL-8, IL-12 and TNFα. Instead, release of the immunregulatory cytokine IL-10 and expression of CD163, both markers specific for anti-inflammatory M2 macrophages (M2), were induced. We conclude that aECMs composed of collagen I and high sulfated HA possess immunomodulating capacities and skew monocyte to macrophage differentiation induced by pro-inflammatory signals of sterile injury toward M2 polarization suggesting them as an effective coating for biomaterials to improve their integration.

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