ROLE FOR INTERLEUKIN-4 IN FOREIGN-BODY GIANT-CELL FORMATION ON A POLY(ETHERURETHANE UREA) IN-VIVO
ROLE FOR INTERLEUKIN-4 IN FOREIGN-BODY GIANT-CELL FORMATION ON A POLY(ETHERURETHANE UREA) IN-VIVO
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DOI：
10.1002/jbm.820291014
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发表时间：
1995-10-01
期刊：
影响因子：
--
通讯作者：
ANDERSON, JM
中科院分区：
文献类型：
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作者：
KAO, WYJ;MCNALLY, AK;ANDERSON, JM
白介素4(IL-4)在体外可诱导巨噬细胞广泛融合形成异物巨细胞(FBGCs)。在目前的研究中，我们的目标是将这些发现扩展到生物材料的体内测试环境中。为了阐明IL-4在体内介导FBGC形成中的作用，对小鼠的皮下支架-植入系统进行了改进。含有聚醚氨酯尿素(PEUA‘)的笼子和空白笼子对照组的渗出白细胞浓度显示出相似的炎症反应，并在移植后14天转为消退，从而证实了笼子-植入系统在小鼠中的适用性。FBGC动力学分析表明，小鼠FBGCs的形成是通过黏附的巨噬细胞以恒定的速度融合而发生的，直到植入14d。将纯化的羊抗鼠IL-4中和抗体(IL4Ab)或正常山羊非特异性对照免疫球蛋白(GtIgG)或重组小鼠IL-4(muIL-4)按不同浓度注入含PEUA‘的笼内，每隔2天注射一次，连续7天。与非特异性Ig G或PBS注射对照组相比，注射IL4Ab可显著降低PEUA笼植入小鼠的FBGC密度。相反，与非特异性免疫球蛋白和PBS注射对照组相比，注射muIL4可显著增加FBGC的密度。黏附巨噬细胞密度、FBGC形态、FBGC平均大小和大小分布在IL4Ab组、非特异性对照gtIg G组、muIL4组和PBS对照组之间无显著差异。我们的数据提示IL-4在体内参与了生物材料表面FBGC的形成。(C)1995 John Wiley&Sons，Inc.
Interleukin-4 (IL-4) was previously shown to induce extensive macrophage fusion to form foreign-body giant cells (FBGCs) in vitro. In the present study, our goal was to extend these findings to an in vivo test environment on biomaterials. The subcutaneous cage-implant system was modified for mice to elucidate IL-4 participation in mediating FBGC formation in vivo. Exudate leukocyte concentrations from cages containing poly(etherurethane urea) (PEUU A') and empty cage controls indicated a similar inflammatory response that turned toward resolution by 14 days postimplantation, thus confirming the applicability of the cage-implant system in mice. FBGC kinetic analysis showed that the formation of mouse FBGCs occurs through the fusion of adherent macrophages at a constant rate up to 14 days of implantation. Purified goat anti-mouse IL-4 neutralizing antibody (IL4Ab) or normal goat nonspecific control IgG (gtIgG) at various concentrations, or recombinant murine IL-4 (muIL4) was injected into the implanted cages containing PEUU A' every 2 days for 7 days. The injection of IL4Ab significantly decreased the FBGC density on PEUU A' cage-implanted in mice, when compared with the nonspecific IgG or PBS injection controls. Conversely, the FBGC density was significantly increased by the injection of muIL4 when compared with nonspecific IgG and PBS injection controls. Adherent macrophage density, FBGC morphology, FBGC average size, and size distribution were not significantly different among IL4Ab, nonspecific control gtIgG, muIL4, and PBS control groups. Our data suggest that IL-4 participates in FBGC formation on biomaterials in vivo. (C) 1995 John Wiley & Sons, Inc.