Novel Role for Mast Cells in Omental Tissue Remodeling and Cell Recruitment in Experimental Peritoneal Dialysis

Abstract

Because of its dynamic structure, the omentum plays a key role in the immunity of the peritoneal cavity by orchestrating peritoneal cell recruitment. Because mast cells accumulate in the omentum upon experimental peritoneal dialysis (PD) and may produce angiogenic/profibrotic factors, it was hypothesized that mast cells mediate omental tissue remodeling during PD. Daily treatment with conventional PD fluid (PDF) for 5 wk resulted in a strong omental remodeling response, characterized by an approximately 10-fold increase in mast cell density (P < 0.01), an approximately 20-fold increase in vessel density (P < 0.02), an approximately 20-fold increase in the number of milky spots (P < 0.01), and a four-fold increase in submesothelial matrix thickness (P < 0.0003) in wild-type rats. In contrast, all PDF-induced omental changes were significantly reduced in mast cell-deficient Ws/Ws rats or in wild-type rats that were treated orally with a mast cell stabilizer cromoglycate. A time-course experiment showed mast cell accumulation immediately before the formation of blood vessels and milky spots. Functionally, PDF evoked a peritoneal cell influx, which was significantly reduced in Ws/Ws rats (P < 0.04) and in wild-type rats that were treated with cromoglycate (P < 0.03). Cromoglycate treatment also completely prevented PDF-induced omental adhesions to the catheter tip (P ‫؍‬ 0.0002). Mesothelial damage, angiogenesis, and fibrosis of mesentery and parietal peritoneum as well as glucose absorption rate and ultrafiltration capacity proved to be mast cell independent. Data strongly support the hypothesis that mast cells mediate PDF-induced omental tissue remodeling and, subsequently, peritoneal cell influx and adhesion formation, providing therapeutic possibilities of modulating omental function.

Angiogenesis in Peritoneal Dialysis

“…Together with previous studies, in which mast-cell-deficient rats also showed significantly reduced angiogenesis in the omentum and in which strong correlations between omental angiogenesis and mast cells have been found, this suggests an important role for mast cells in new blood vessel formation upon PD [41] .…”

“…The mast cells are found near blood vessels and the number of mast cells in the omentum strongly correlates with the number of blood vessels. PDF exposure in mast cell-depleted wild-type rats and mast cell-deficient Ws/Ws rats shows a significant reduction in omental angiogenesis also indicating a compelling role for mast cells in PD-induced angiogenesis [41] .…”

Mast cells aggravate sepsis by inhibiting peritoneal macrophage phagocytosis

“…IL-4 is a pleiotropic cytokine with major immune regulatory functions, such as in naive T cell differentiation and Th2 polarization (48), alternative macrophage (M2 macrophage) differentiation, and proliferation of tissue-resident macrophages (49), ultimately playing an important role in tissue homeostasis and repair (32,50). Of note, mast cells are essential for the differentiation of macrophages in milky spots of the peritoneal omentum, known to play an important role in pathogen elimination (51). Low amounts of bacteria or endotoxins may diffuse from the gut under steadystate conditions to weakly stimulate PMCs, thereby allowing the proliferation of resident macrophages and maintaining resident cell homeostasis and peritoneal tissue integrity.…”

Mast cells in peritoneal fluid in rats with experimentally induced peritoneal adhesions.

“…It is likely that the activity of cellular mediators in the peritoneal fluid plays an active role in peritoneal healing. These cellular mediators are produced by the cellular components of the peritoneal fluid such as the mast cells, the macrophages, the neutrophils and the eosinophils [10,11]. Surgical trauma triggers inflammation process which causes an increase in vascular permeability and release of fibrinrich exudates [12].…”