Macrophage-Mediated Phagocytosis and Dissolution of Amyloid-Like Fibrils in Mice, Monitored by Optical Imaging.

Macrophage-Mediated Phagocytosis and Dissolution of Amyloid-Like Fibrils in Mice, Monitored by Optical Imaging. Am J Pathol. 2019 Feb 05;: Authors: Richey T, Foster JS, Williams AD, Williams AB, Stroh A, Macy S, Wooliver C, Heidel RE, Varanasi SK, Ergen EN, Trent DJ, Kania SA, Kennel SJ, Martin EB, Wall JS Abstract Light chain-associated amyloidosis is characterized by the extracellular deposition of amyloid fibrils in abdominothoracic organs, skin, soft tissue, and peripheral nerves. Phagocytic cells of the innate immune system appear to be ineffective at clearing the material; however, human light chain amyloid extract, injected subcutaneously into mice, is rapidly cleared in a process that requires neutrophil activity. To better elucidate the phagocytosis of light chain fibrils, a potential method of cell-mediated dissolution, amyloid-like fibrils were labeled with the pH-sensitive dye pHrodo red and a near infrared fluorophore. After injecting this material subcutaneously in mice, optical imaging was used to quantitatively monitor phagocytosis and dissolution of fibrils concurrently. Histological evaluation of the residual fibril masses revealed the presence of CD68+, F4/80+, Iba-1- macrophages containing Congo red-stained fibrils as well as neutrophil-associated proteins with no evidence of intact neutrophils. These data suggest an early infiltration of neutrophils followed by extensive phagocytosis of the light chain fibrils by...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research