RT Journal Article
SR Electronic
T1 Ongoing exposure to peritoneal dialysis fluid alters resident peritoneal macrophage phenotype and activation propensity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.03.02.973404
DO 10.1101/2020.03.02.973404
A1 Tara E. Sutherland
A1 Tovah N. Shaw
A1 Rachel Lennon
A1 Sarah E. Herrick
A1 Dominik Rückerl
YR 2020
UL http://biorxiv.org/content/early/2020/03/18/2020.03.02.973404.abstract
AB 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 cost. However, longterm 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. Thus, alterations in tissue resident macrophages may render longterm PD patients sensitive to developing peritonitis and consequently fibrosis/sclerosis.