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

Tina Richey, James S. Foster, Angela D. Williams, Anna B. Williams, Alexa Stroh, Sallie Macy, Craig Wooliver, Robert Heidel, Siva K. Varanasi, Elizabeth N. Ergen, Dianne J. Trent, Stephen A. Kania, Stephen Kennel, Emily Martin, Jonathan Wall

Research output: Contribution to journalArticle

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. Histologic evaluation of the residual fibril masses revealed the presence of CD68 + , F4/80 + , ionized calcium binding adaptor molecule 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 macrophages, leading to dissolution of the mass. Optical imaging of this novel murine model, coupled with histologic evaluation, can be used to study the cellular mechanisms underlying dissolution of synthetic amyloid-like fibrils and human amyloid extracts. In addition, it may serve as a test bed to evaluate investigational opsonizing agents that might serve as therapeutic agents for light chain–associated amyloidosis.

Original languageEnglish (US)
Pages (from-to)989-998
Number of pages10
JournalAmerican Journal of Pathology
Volume189
Issue number5
DOIs
StatePublished - May 1 2019

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Optical Imaging
Phagocytosis
Amyloid
Macrophages
Light
Neutrophils
Amyloidosis
Congo
Neutrophil Infiltration
Phagocytes
Peripheral Nerves
Immune System
Coloring Agents
Calcium
Skin
Proteins

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Macrophage-Mediated Phagocytosis and Dissolution of Amyloid-Like Fibrils in Mice, Monitored by Optical Imaging. / Richey, Tina; Foster, James S.; Williams, Angela D.; Williams, Anna B.; Stroh, Alexa; Macy, Sallie; Wooliver, Craig; Heidel, Robert; Varanasi, Siva K.; Ergen, Elizabeth N.; Trent, Dianne J.; Kania, Stephen A.; Kennel, Stephen; Martin, Emily; Wall, Jonathan.

In: American Journal of Pathology, Vol. 189, No. 5, 01.05.2019, p. 989-998.

Research output: Contribution to journalArticle

Richey, T, Foster, JS, Williams, AD, Williams, AB, Stroh, A, Macy, S, Wooliver, C, Heidel, R, Varanasi, SK, Ergen, EN, Trent, DJ, Kania, SA, Kennel, S, Martin, E & Wall, J 2019, 'Macrophage-Mediated Phagocytosis and Dissolution of Amyloid-Like Fibrils in Mice, Monitored by Optical Imaging', American Journal of Pathology, vol. 189, no. 5, pp. 989-998. https://doi.org/10.1016/j.ajpath.2019.01.011
Richey, Tina ; Foster, James S. ; Williams, Angela D. ; Williams, Anna B. ; Stroh, Alexa ; Macy, Sallie ; Wooliver, Craig ; Heidel, Robert ; Varanasi, Siva K. ; Ergen, Elizabeth N. ; Trent, Dianne J. ; Kania, Stephen A. ; Kennel, Stephen ; Martin, Emily ; Wall, Jonathan. / Macrophage-Mediated Phagocytosis and Dissolution of Amyloid-Like Fibrils in Mice, Monitored by Optical Imaging. In: American Journal of Pathology. 2019 ; Vol. 189, No. 5. pp. 989-998.
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