The resident macrophages in murine pancreatic islets are constantly probing their local environment, capturing beta cell granules and blood particles.

Authors

Bernd H Zinselmeyer
Anthony N Vomund
Brian T Saunders
Michael W. Johnson MD., PhD, Lehigh Valley NetworkFollow
Javier A Carrero
Emil R Unanue

Publication/Presentation Date

6-1-2018

Abstract

AIMS/HYPOTHESIS: We studied here the interactions between the resident macrophages of pancreatic islets with beta cells and the blood vasculature. We also examined the immunological consequences of such interactions.

METHODS: Islets were isolated from C57BL/6 mice expressing CX3C motif chemokine receptor 1-green fluorescent protein (CX3CR-GFP) and examined live by two-photon microscopy. Islets were also examined by electron microscopy to study the relationship of the intra-islet macrophages with the beta cells. In NOD.Rag1

RESULTS: Two-photon microscopy showed that the islet resident macrophages were in close contact with blood vessels and had extensive filopodial activity. Some filopodia had direct access to the vessel lumen and captured microparticles. Addition of glucose at high concentration reduced the degree of filopodia sampling of islets. This finding applied to in vivo injection of glucose or to in vitro cultures. Ultrastructural examination showed the close contacts of macrophages with beta cells. Such macrophages contained intact dense core granules. Functional studies in NOD mice indicated that the macrophages presented insulin peptides to insulin-reactive T cells. Presentation was increased after glucose challenge either ex vivo or after an in vivo pulse. In agreement with the morphological findings, presentation was not affected by insulin receptor blockade.

CONCLUSIONS/INTERPRETATION: Islet resident macrophages are highly active, sampling large areas of the islets and blood contents and capturing beta cell granules. After such interactions, macrophages present immunogenic insulin to specific autoreactive T cells.

Volume

61

Issue

6

First Page

1374

Last Page

1383

ISSN

1432-0428

Published In/Presented At

Zinselmeyer, B. H., Vomund, A. N., Saunders, B. T., Johnson, M. W., Carrero, J. A., & Unanue, E. R. (2018). The resident macrophages in murine pancreatic islets are constantly probing their local environment, capturing beta cell granules and blood particles. Diabetologia, 61(6), 1374–1383. https://doi.org/10.1007/s00125-018-4592-4

Disciplines

Medicine and Health Sciences

PubMedID

29589072

Department(s)

Department of Pathology and Laboratory Medicine

Document Type

Article