Secretion of a chemotactic substance(s) by AGE-stimulated human monocytes.

Receptors for products of non-enzymatic glycosylation have been identified previously on activated human monocytes. In this study we have found that medium conditioned by activated human monocytes following stimulation with AGE-BSA elicited an almost 3-fold greater chemotactic response from other activated monocytes than conditioned medium obtained following stimulation with control BSA (44 +/- 13 and 16 +/- 4.6, respectively; n = 9, P less than 0.05). The response elicited from AGE-BSA alone was not statistically significant. It appears that stimulation of the cells via the AGE-receptor results in the secretion of increased levels of a chemotactic substance(s) for monocytes/macrophages. This mechanism may help to explain the pathogenesis of atherosclerosis in diabetes, as monocyte accumulation within the vessel wall is an important step in fatty streak development.