Studies on the mechanisms of leukocyte adhesion to cellulose acetate beads: An in vitro model to assess the efficacy of cellulose acetate carrier-based granulocyte and monocyte adsorptive apheresis
Studies on the mechanisms of leukocyte adhesion to cellulose acetate beads: An in vitro model to assess the efficacy of cellulose acetate carrier-based granulocyte and monocyte adsorptive apheresis
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DOI：
10.1046/j.1526-0968.2003.00049.x
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发表时间：
2003-06-01
影响因子：
1.9
通讯作者：
Adachi, M
中科院分区：
文献类型：
--
作者：
Hiraishi, K;Takeda, Y;Adachi, M
粒细胞和单核细胞吸附分离(GMA)使用填充醋酸纤维素(CA)珠(载体)的柱(载体)对类风湿性关节炎和溃疡性结肠炎患者具有显著的临床疗效。为了进一步了解基于醋酸纤维素载体的GMA改善疾病的机制，在本研究中，我们研究了在受控条件下，人外周血在37℃下暴露于载体长达60分钟后，粒细胞和单核细胞与CA珠子的黏附机制。醋酸纤维微球选择性吸附粒细胞、单核细胞、CD19(+)(B细胞)和CD56(+)(NK细胞)淋巴细胞亚群。热灭活血浆和EDTA可抑制粒细胞和单核细胞的吸附，说明这种吸附是血浆蛋白(免疫球蛋白、补体)和钙依赖的。相应地，通过在载体上包覆一层免疫球蛋白来显著增强粒细胞和单核细胞的吸附。类似地，C3b被吸附在CA小球上，作为补体激活的标志。结果表明，免疫球蛋白和活性补体片段通过FcGammaR和/或类似CR3的白细胞补体受体介导白细胞与CA小球的黏附。此外，CA珠能诱导CD16(+)粒细胞和CD14(+)单核细胞表达肿瘤坏死因子受体，但不能诱导CD3(+)淋巴细胞表达。综上所述，CA小球可能是一种合适的诱导体外免疫调节的生物材料，用于治疗与病理性白细胞活性相关的自身免疫性疾病。
Granulocyte and monocyte adsorptive apheresis (GMA) using a column filled with cellulose acetate (CA) beads (carriers) has been associated with a significant clinical efficacy in patients with rheumatoid arthritis and ulcerative colitis. To obtain further understanding on the mechanisms of disease modification by cellulose acetate-carrier-based GMA, in the present study, we investigated the mechanisms of granulocyte and monocyte adhesion to CA beads following exposure of human peripheral blood to the carriers at 37degreesC for up to 60 min under controlled conditions. Cellulose acetate beads selectively adsorbed granulocytes, monocytes, CD19(+) (B cells) and CD56(+) (NK cells) lymphocyte subpopulations. The granulocyte and monocyte adsorption was inhibited by heat-inactivated plasma and EDTA, indicating that the adsorption was plasma protein (immunoglobulin, complement) and calcium dependent. Accordingly, granulocyte and monocyte adsorption was markedly enhanced by coating the carriers with IgG. Similarly, C3b was adsorbed onto the CA beads as a marker of complement activation. The results indicated that IgG and active complement fragments mediated leukocyte adhesion to CA beads via the FcgammaR and/or leukocyte complement receptor like CR3. Additionally, CA beads induced loss of expression of TNF receptors on CD16(+) granulocytes and CD14(+) monocytes, but not on CD3(+) lymphocytes. In conclusion, CA beads might be an appropriate biomaterial for inducing extracorporeal immunomodulation as a treatment for auto-immune diseases which are associated with pathological leukocyte activity.