先前研究已經指出紅斑性狼瘡自體抗原的產生和此類病人凋亡細胞的清除不全有關。而殼胺醯胺轉移脢, 本身為一個需鈣離子之轉胺甲醯轉移脢﹐也被證實牽涉在紅斑性狼瘡的致病基轉中。然而﹐我們在狼瘡模式小鼠中﹐並沒有發現殼胺醯胺轉移脢有明顯的表現差異﹐但是此類小鼠之巨嗜細胞的吞噬能力﹐跟對照之正常小鼠比較﹐卻有明顯的下降。為了找出更確切的原因﹐本年度針對狼瘡模式小鼠的巨嗜細胞﹐找出可能造成吞噬能力下降的原因。我們的實驗結果發現﹐粒線體相關路徑的細胞凋亡蛋白﹐在狼瘡模式小鼠有較明顯增加。這些發現也說明小鼠之巨嗜細胞的吞噬能力較低是因為自身凋亡所致。
Previous reports have suggested a connection between defective clearance of apoptotic cells in systemic lupus erythematosus (SLE) and the generation of autoantigens. Transglutaminase 2 (TG2), an inducible transamidating acyltransferase that catalyzes calcium-dependent protein modification, is involved in the pathogenesis of SLE. However, no obvious variation of TG2 expression among BALB/c, MRL and NZB mice was observed and association between TG2 expression and phagocytic ability. In this year, for further examine the possible mechanism involved in the impaired phagocytic ability of macrophages, we designed to examine whether the known association of TG2 with apoptosis and apoptotic clearance might explain its role in SLE. Our experimental results demonstrated that decreased phagocytic ability in macrophages of NZB/W mice was not associated with changes in expression of TG2 (mRNA or protein), but was associated with increased TG2 activity, increased caspase 3 activity, and increased expression of the pro-apoptotic proteins Bax and Apaf-1. This finding may account for the decreased phagocytic ability of macrophages in SLE mice.
