Complement inhibition reduces material-induced leukocyte activation with PEG modified polystyrene beads (Tentagel™) but not polystyrene beads
Complement inhibition reduces material-induced leukocyte activation with PEG modified polystyrene beads (Tentagel™) but not polystyrene beads
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DOI：
10.1002/jbm.a.30354
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发表时间：
2005-09-15
影响因子：
4.9
通讯作者：
Sefton, MV
中科院分区：
文献类型：
--
作者：
Gorbet, MB;Sefton, MV
在分离的白细胞中，用聚乙二醇改性的聚苯乙烯小球(PSPEG)抑制补体减少材料诱导的白细胞活化(CD11b)，但不能用聚苯乙烯小球(PS)。根据SC5b-9水平的测定，PS-PEG微球(TentaGel(TM))具有补体激活作用，这与这些微球对补体抑制剂抑制白细胞的敏感性一致。与PS和PS-PEG珠接触后，分离的血浆和血小板中的白细胞显著上调CD11b，而TF的表达和磷脂酰丝氨酸的暴露保持在本底水平。SCR1对补体的抑制作用部分降低了PS-PEG微球上CD11b的表达，但对PS微球无影响。吡哆醛-5-磷酸(P5P)能够显著减少CD11b的上调和PS-PEG微珠对磷脂酰丝氨酸的暴露，尽管它似乎不能抑制SC5b-9的产生。戊二氮和NAAGA可抑制补体，并能有效地抑制PS和PS-PEG对CD11b的上调。然而，它们也对白细胞信号机制有抑制作用，排除了它们在这方面的进一步研究的有效性。PS和PS-聚乙二醇珠上的白细胞黏附程度相似。虽然sCR1和P5P阻断了黏附在PS-聚乙二醇珠上的白细胞的黏附和激活，但它们对黏附在PS微珠上的白细胞没有影响。补体在白细胞激活和黏附中的作用被发现是物质依赖的。因此，在某些情况下，但不是所有情况下，可以通过抑制补体来解决白细胞-材料相容性。对于这些其他材料(这里的例子是PS)，可能需要利用其他机制，如纤维蛋白原吸附和直接释放白细胞，以最大限度地减少白细胞的激活和黏附。(C)2005年威利期刊公司。
With isolated leukocytes, inhibiting complement reduced material-induced leukocyte activation (CD11b) with polyethylene glycol modified polystyrene beads (PSPEG), but not with polystyrene beads (PS). The PS-PEG beads (TentaGel (TM)) were complement activating as measured by SC5b-9 levels consistent with the sensitivity of these beads to leukocyte inhibition with complement inhibitors. Following contact with PS and PS-PEG beads, isolated leukocytes in plasma and in the absence in platelets were found to significantly upregulate CD11b, while TF expression and exposure of phosphatidylserine remained at background levels. Complement inhibition by means of sCR1 partially reduced CD11b upregulation on PS-PEG beads, but had no effect with PS beads. Pyridoxal-5-phosphate (P5P) was able to significantly reduce both CD11b upregulation and exposure of phosphatidylserine with PS-PEG beads, although it did not appear to inhibit SC5b-9 production. Pentamidine and NAAGA inhibited complement and were effective in reducing CD11b upregulation with both PS and PS-PEG. However, they also had an inhibitory effect on leukocyte signaling mechanisms, precluding their utility for further study in this context. Leukocyte adhesion occurred to similar extents on both PS and PS-PEG beads. While sCR1 and P5P blocked adhesion and activation (for adherent leukocytes) on PS-PEG beads, they had no effect on leukocytes adherent to PS beads. The role of complement in leukocyte activation and adhesion was found to be material-dependent. Thus, leukocyte-material compatibility may be resolved by complement inhibition in some but not all cases. For these other materials (example here was PS), other mechanisms, such as fibrinogen adsorption and direct leukocyte release, may need exploitation to minimize leukocyte activation and adhesion. (c) 2005 Wiley Periodicals, Inc.