Matheson Loren A, Santerre J Paul, Labow Rosalind S
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
J Cell Physiol. 2004 Apr;199(1):8-19. doi: 10.1002/jcp.10412.
Monocytes are recruited to the material surface of an implanted biomedical device recognizing it as a foreign body. Differentiation into macrophages subsequently occurs followed by fusion to form foreign body giant cells (FBGCs). Consequently, implants can become degraded, cause chronic inflammation or become isolated by fibrous encapsulation. In this study, a relationship between material surface chemistry and the FBGC response was demonstrated by seeding mature monocyte-derived macrophages (MDMs) on polycarbonate-based polyurethanes that differed in their chemical structures (synthesized with poly(1,6-hexyl 1,2-ethyl carbonate) diol, and either (14)C-hexane diisocyanate and butanediol (BD) (referred to as HDI) or 4,4'-methylene bisphenyl diisocyanate and (14)C-BD (referred to as MDI)) and material degradation assessed. At 48 h of cell-material interaction, the FBGC attached to HDI were more multinucleated (73%) compared to MDI or the polystyrene (PS) control (21 and 36%, respectively). There was a fivefold increase in the synthesis and secretion of a protein with an approximate molecular weight of 48 kDa and a pI of 6.1 (determined by two-dimensional gel electrophoresis) only from cells seeded on HDI. Immunoprecipitation confirmed that MSE and CE were synthesized and secreted de novo. Immunoblotting also showed an increase in secreted monocyte-specific esterase (MSE) and cholesterol esterase (CE) from cells seeded on HDI relative to PS and MDI. Significantly more radiolabel ((14)C) release and esterase activity were elicited by MDMs on HDI than MDI (P < 0.05). The material that was more degradable (HDI), elicited greater protein synthesis and esterase secretion as well as more multinucleated MDMs than MDI, suggesting that the material surface chemistry modulates the function of MDM at the site of an inflammatory response to an implanted device.
单核细胞被招募到植入生物医学装置的材料表面，将其识别为异物。随后单核细胞分化为巨噬细胞，接着融合形成异物巨细胞（FBGCs）。因此，植入物可能会降解、引发慢性炎症或被纤维包裹隔离。在本研究中，通过将成熟的单核细胞衍生巨噬细胞（MDMs）接种在化学结构不同的聚碳酸酯基聚氨酯上（用聚（1,6 - 己基1,2 - 碳酸乙酯）二醇与（14）C - 己烷二异氰酸酯和丁二醇（BD）（称为HDI）或4,4'-亚甲基双苯基二异氰酸酯和（14）C - BD（称为MDI）合成），并评估材料降解情况，证明了材料表面化学与FBGC反应之间的关系。在细胞与材料相互作用48小时时，与MDI或聚苯乙烯（PS）对照（分别为21%和36%）相比，附着在HDI上的FBGC多核化程度更高（73%）。仅接种在HDI上的细胞合成并分泌了一种分子量约为48 kDa、pI为6.1的蛋白质（通过二维凝胶电泳测定），其合成和分泌增加了五倍。免疫沉淀证实MSE和CE是重新合成并分泌的。免疫印迹还显示，相对于PS和MDI，接种在HDI上的细胞分泌的单核细胞特异性酯酶（MSE）和胆固醇酯酶（CE）增加。MDMs在HDI上引发的放射性标记（（14）C）释放和酯酶活性显著高于MDI（P < 0.05）。更易降解的材料（HDI）比MDI引发了更大的蛋白质合成和酯酶分泌，以及更多的多核MDMs，这表明材料表面化学在植入装置炎症反应部位调节MDM的功能。
