AMYLOID PRODUCTION BY HUMAN MONOCYTE CULTURES

摘要

Amyloid formation by mouse peritoneal macrophages cultured in the presence of recombinant mouse SAA1.1 has been described previously (1). We now present human monocytes isolated from peripheral blood as an alternative cell culture model. In contrast to in vitro (test tube) studies, amyloid formation in macrophage and monocyte cultures occurs under physiologic conditions, i.e., cells are maintained in neutral pH medium containing SAA at a concentration typical of that seen in acute phase serum (150 ng/ml). By using these model systems, events in AA amyloid pathogenesis, and importantly those initiating formation of an amyloid nidus, can be studied at the level of individual cells and before extracellular deposition and possible resorptbn have become confounding issues. Amyloid formation in macrophage and monocyte cultures is accelerated and augmented by, but not dependent on, the addition of amyloid-enhancing factor (AEF), and is accompanied by C-terminal cleavage of SAA. In agreement with previous findings from other laboratories, our data show nascent amyloid formation in lysosome-derived vesicles (2-5). Additionally, our observations suggest that release of these vesicles to the cell surface is an active metabolic process which does not directly result in cell death. The micrographs presented here depict monocytes engaged in various stages of amyloid formation.