Cargando…

The Peri-islet Basement Membrane, a Barrier to Infiltrating Leukocytes in Type 1 Diabetes in Mouse and Human

We provide the first comprehensive analysis of the extracellular matrix (ECM) composition of peri-islet capsules, composed of the peri-islet basement membrane (BM) and subjacent interstitial matrix (IM), in development of type 1 diabetes in NOD mice and in human type 1 diabetes. Our data demonstrate...

Descripción completa

Detalles Bibliográficos
Autores principales: Korpos, Éva, Kadri, Nadir, Kappelhoff, Reinhild, Wegner, Jeannine, Overall, Christopher M., Weber, Ekkehard, Holmberg, Dan, Cardell, Susanna, Sorokin, Lydia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554379/
https://www.ncbi.nlm.nih.gov/pubmed/23139348
http://dx.doi.org/10.2337/db12-0432
_version_ 1782256884911177728
author Korpos, Éva
Kadri, Nadir
Kappelhoff, Reinhild
Wegner, Jeannine
Overall, Christopher M.
Weber, Ekkehard
Holmberg, Dan
Cardell, Susanna
Sorokin, Lydia
author_facet Korpos, Éva
Kadri, Nadir
Kappelhoff, Reinhild
Wegner, Jeannine
Overall, Christopher M.
Weber, Ekkehard
Holmberg, Dan
Cardell, Susanna
Sorokin, Lydia
author_sort Korpos, Éva
collection PubMed
description We provide the first comprehensive analysis of the extracellular matrix (ECM) composition of peri-islet capsules, composed of the peri-islet basement membrane (BM) and subjacent interstitial matrix (IM), in development of type 1 diabetes in NOD mice and in human type 1 diabetes. Our data demonstrate global loss of peri-islet BM and IM components only at sites of leukocyte infiltration into the islet. Stereological analyses reveal a correlation between incidence of insulitis and the number of islets showing loss of peri-islet BM versus islets with intact BMs, suggesting that leukocyte penetration of the peri-islet BM is a critical step. Protease- and protease inhibitor–specific microarray analyses (CLIP-CHIP) of laser-dissected leukocyte infiltrated and noninfiltrated pancreatic islets and confirmatory quantitative real time PCR and protein analyses identified cathepsin S, W, and C activity at sites of leukocyte penetration of the peri-islet BM in association with a macrophage subpopulation in NOD mice and human type 1 diabetic samples and, hence, potentially a novel therapeutic target specifically acting at the islet penetration stage. Interestingly, the peri-islet BM and underlying IM are reconstituted once inflammation subsides, indicating that the peri-islet BM-producing cells are not lost due to the inflammation, which has important ramifications to islet transplantation studies.
format Online
Article
Text
id pubmed-3554379
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher American Diabetes Association
record_format MEDLINE/PubMed
spelling pubmed-35543792014-02-01 The Peri-islet Basement Membrane, a Barrier to Infiltrating Leukocytes in Type 1 Diabetes in Mouse and Human Korpos, Éva Kadri, Nadir Kappelhoff, Reinhild Wegner, Jeannine Overall, Christopher M. Weber, Ekkehard Holmberg, Dan Cardell, Susanna Sorokin, Lydia Diabetes Islet Studies We provide the first comprehensive analysis of the extracellular matrix (ECM) composition of peri-islet capsules, composed of the peri-islet basement membrane (BM) and subjacent interstitial matrix (IM), in development of type 1 diabetes in NOD mice and in human type 1 diabetes. Our data demonstrate global loss of peri-islet BM and IM components only at sites of leukocyte infiltration into the islet. Stereological analyses reveal a correlation between incidence of insulitis and the number of islets showing loss of peri-islet BM versus islets with intact BMs, suggesting that leukocyte penetration of the peri-islet BM is a critical step. Protease- and protease inhibitor–specific microarray analyses (CLIP-CHIP) of laser-dissected leukocyte infiltrated and noninfiltrated pancreatic islets and confirmatory quantitative real time PCR and protein analyses identified cathepsin S, W, and C activity at sites of leukocyte penetration of the peri-islet BM in association with a macrophage subpopulation in NOD mice and human type 1 diabetic samples and, hence, potentially a novel therapeutic target specifically acting at the islet penetration stage. Interestingly, the peri-islet BM and underlying IM are reconstituted once inflammation subsides, indicating that the peri-islet BM-producing cells are not lost due to the inflammation, which has important ramifications to islet transplantation studies. American Diabetes Association 2013-02 2013-01-17 /pmc/articles/PMC3554379/ /pubmed/23139348 http://dx.doi.org/10.2337/db12-0432 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Islet Studies
Korpos, Éva
Kadri, Nadir
Kappelhoff, Reinhild
Wegner, Jeannine
Overall, Christopher M.
Weber, Ekkehard
Holmberg, Dan
Cardell, Susanna
Sorokin, Lydia
The Peri-islet Basement Membrane, a Barrier to Infiltrating Leukocytes in Type 1 Diabetes in Mouse and Human
title The Peri-islet Basement Membrane, a Barrier to Infiltrating Leukocytes in Type 1 Diabetes in Mouse and Human
title_full The Peri-islet Basement Membrane, a Barrier to Infiltrating Leukocytes in Type 1 Diabetes in Mouse and Human
title_fullStr The Peri-islet Basement Membrane, a Barrier to Infiltrating Leukocytes in Type 1 Diabetes in Mouse and Human
title_full_unstemmed The Peri-islet Basement Membrane, a Barrier to Infiltrating Leukocytes in Type 1 Diabetes in Mouse and Human
title_short The Peri-islet Basement Membrane, a Barrier to Infiltrating Leukocytes in Type 1 Diabetes in Mouse and Human
title_sort peri-islet basement membrane, a barrier to infiltrating leukocytes in type 1 diabetes in mouse and human
topic Islet Studies
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554379/
https://www.ncbi.nlm.nih.gov/pubmed/23139348
http://dx.doi.org/10.2337/db12-0432
work_keys_str_mv AT korposeva theperiisletbasementmembraneabarriertoinfiltratingleukocytesintype1diabetesinmouseandhuman
AT kadrinadir theperiisletbasementmembraneabarriertoinfiltratingleukocytesintype1diabetesinmouseandhuman
AT kappelhoffreinhild theperiisletbasementmembraneabarriertoinfiltratingleukocytesintype1diabetesinmouseandhuman
AT wegnerjeannine theperiisletbasementmembraneabarriertoinfiltratingleukocytesintype1diabetesinmouseandhuman
AT overallchristopherm theperiisletbasementmembraneabarriertoinfiltratingleukocytesintype1diabetesinmouseandhuman
AT weberekkehard theperiisletbasementmembraneabarriertoinfiltratingleukocytesintype1diabetesinmouseandhuman
AT holmbergdan theperiisletbasementmembraneabarriertoinfiltratingleukocytesintype1diabetesinmouseandhuman
AT cardellsusanna theperiisletbasementmembraneabarriertoinfiltratingleukocytesintype1diabetesinmouseandhuman
AT sorokinlydia theperiisletbasementmembraneabarriertoinfiltratingleukocytesintype1diabetesinmouseandhuman
AT korposeva periisletbasementmembraneabarriertoinfiltratingleukocytesintype1diabetesinmouseandhuman
AT kadrinadir periisletbasementmembraneabarriertoinfiltratingleukocytesintype1diabetesinmouseandhuman
AT kappelhoffreinhild periisletbasementmembraneabarriertoinfiltratingleukocytesintype1diabetesinmouseandhuman
AT wegnerjeannine periisletbasementmembraneabarriertoinfiltratingleukocytesintype1diabetesinmouseandhuman
AT overallchristopherm periisletbasementmembraneabarriertoinfiltratingleukocytesintype1diabetesinmouseandhuman
AT weberekkehard periisletbasementmembraneabarriertoinfiltratingleukocytesintype1diabetesinmouseandhuman
AT holmbergdan periisletbasementmembraneabarriertoinfiltratingleukocytesintype1diabetesinmouseandhuman
AT cardellsusanna periisletbasementmembraneabarriertoinfiltratingleukocytesintype1diabetesinmouseandhuman
AT sorokinlydia periisletbasementmembraneabarriertoinfiltratingleukocytesintype1diabetesinmouseandhuman