An autoantibody against Nε-(carboxyethyl)lysine (CEL): Possible involvement in the removal of CEL-modified proteins by macrophages

Advanced glycation end products (AGEs) are believed to play a significant role in the development of diabetic complications. In this study, we measured the levels of autoantibodies against several AGE structures in healthy human plasma and investigated the physiological role of the autoantibodies. A high titer of the autoantibody against Nε-(carboxyethyl)lysine (CEL) was detected in human plasma compared with other AGE structures such as CML and pentosidine. The purified human anti-CEL autoantibody reacted with CEL-modified human serum albumin (CEL-HSA), but not CML-HSA. A rabbit polyclonal anti-CEL antibody, used as a model autoantibody against CEL, accelerated the uptake of CEL-HSA by macrophages, but did not enhance the uptake of native HSA. Furthermore, when 125I-labeled CEL-HSA was injected into the tail vein of mice, accumulation of 125I-CEL-HSA in the liver was accelerated by co-injection of the rabbit anti-CEL antibody. These results demonstrate that the autoantibody against CEL in plasma may play a role in the macrophage uptake of CEL-modified proteins.

► A higher amount of autoantibody against CEL than that of other AGEs was observed in human plasma.
► The purified human anti-CEL autoantibody specifically reacted with CEL.
► Anti-CEL antibody accelerated the uptake of 125I-CEL-HSA by macrophage in vitro.
► Endocytic uptake of 125I-CEL-HSA by mice liver was accelerated in the presence of anti-CEL antibody.