Abstract
Peritoneal dialysis (PD) is a more continuous alternative to haemodialysis, for patients with chronic kidney disease, with considerable initial benefits for survival, patient independence and healthcare costs. However, long-term PD is associated with significant pathology, negating the positive effects over haemodialysis. Importantly, peritonitis and activation of macrophages is closely associated with disease progression and treatment failure. However, recent advances in macrophage biology suggest opposite functions for macrophages of different cellular origins. While monocyte-derived macrophages promote disease progression in some models of fibrosis, tissue resident macrophages have rather been associated with protective roles. Thus, we aimed to identify the relative contribution of tissue resident macrophages to PD induced inflammation in mice. Unexpectedly, we found an incremental loss of homeostatic characteristics, anti-inflammatory and efferocytic functionality in peritoneal resident macrophages, accompanied by enhanced inflammatory responses to external stimuli. Moreover, presence of glucose degradation products within the dialysis fluid led to markedly enhanced inflammation and almost complete disappearance of tissue resident cells. Thus, alterations in tissue resident macrophages may render long-term PD patients sensitive to developing peritonitis and consequently fibrosis/sclerosis.
Original language | English |
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Article number | 715209 |
Number of pages | 15 |
Journal | Frontiers in Immunology |
Volume | 12 |
DOIs | |
Publication status | Published - 27 Jul 2021 |
Bibliographical note
Funding Information: We thank Dr. Gareth Howell from the Flow Cytometry Core Facility at the University of Manchester for assistance with the flow cytometry analyses. We?d also like to thank Sister Trish Smith from the Royal Manchester Children?s Hospital for the provision of Physioneal 40, Dr John Grainger (University of Manchester, UK) for the provision of the Cx3cr1CreER:R26-eyfp mice as well as Prof. Judith E. Allen (University of Manchester, UK) for use of her Home Office animal licence and critical appraisal of the work. This manuscript was deposited as a pre-print version on BioRxiv prior to peer review (90). Publisher Copyright: © Copyright © 2021 Sutherland, Shaw, Lennon, Herrick and Rückerl.Keywords
- fibrosis
- glucose degradation product
- inflammation
- macrophage
- peritoneal dialysis
- tissue resident