Mesothelial cells can detach from the mesentery and differentiate into macrophage-like cells

Abstract

Peritoneal cell suspension is composed of heterogeneous cell population. Macrophages are the most numerous cells among them. They can originate from different sources and can be resident, exudate and elicited. When we used Freund's adjuvant to elicit peritoneal macrophages, cells having large amount of caveolae on their plasma membrane appeared in the peritoneal wash. The number of these caveolae-rich cells increased by the time of the Freund's adjuvant treatment. Although their morphology was different form from the common macrophages, they were labelled with pan-macrophage antibodies. As the origin of these cells is unknown in this work, we tried to find out where they can originate from. Our interest turned towards the mesothelial cells. We found that the adjuvant treatment resulted in significant morphological changes in these cells and stimulate them to leave the surface of the mesentery. By the time of the adjuvant treatment, the macrophage markers expression increased in the mesothelial cells and more cells were found to detach from the mesentery. These results strongly suggest that under special stimuli mesothelial cells can leave the mesentery and differentiate into phagocytotic (macrophage-like) cells. These data raises the idea that mesothelial cells might not entirely differentiated and represent a multipotential cell lineage. To study whether this is the case we used anti-nestin antibody, which is a specific marker for multifunctional, multi-lineage progenitor cells. Mesothelial cells showed strong labelling with this antibody indicating that these cells really represent a 'young', not entirely differentiated cell population.

Inflammatory Cytokinesinduce EMT in Mesenteric Mesothelial Cells, and Transdifferentiate Them into Macrophages

“…Type II receptor then trans-phosphorylates (activates) the signalling receptor (type I) that can initiate Smad2/3 signalling pathway. We have previously demonstrated [12] Freund's adjuvant treatment also induced a significant amount of TGF-β production in mesothelial cells that was secreted into the peritoneal cavity. The level of TGF-β highly correlated with the kinetics of the inflammation, and transforming mesothelial cells also expressed TGFβRII [13].…”

“…DURING INFLAMMATION INDUCED EMT During inflammation-induced EMT mesenteric mesothelial cells start to express macrophage markers (OX43, ED1) as well [12,52], suggesting that they might be transformed into macrophage-like cells [53]. Our previous data showed that under inflammatory stimuli the number of peritoneal macrophages dramatically increased [54].…”

“…One candidate of these non-hematopoietic cells are the mesothelial cells that are present all over the peritoneal cavity, covering the internal organs of the abdomen. They express nestin [12], a well-known and characteristic marker of multi-lineage progenitor cells, the presence of which indicates multipotentiality and regenerative capacity [59]. Nestin expression in mesothelial cells clearly shows that they are not terminally differentiated cells;instead, they are multipotent "young" cells with high regenerative capacity and able to differentiate into many types of cells [12].…”

“…They express nestin [12], a well-known and characteristic marker of multi-lineage progenitor cells, the presence of which indicates multipotentiality and regenerative capacity [59]. Nestin expression in mesothelial cells clearly shows that they are not terminally differentiated cells;instead, they are multipotent "young" cells with high regenerative capacity and able to differentiate into many types of cells [12]. The granulocyte-macrophage colony-stimulating factor (GM-CSF) -a member of the hematopoietic cytokine familypromotes the survival and activation of granulocytes, www.wjrr.org macrophages and dendritic cell differentiation in vivo, and it also stimulates proliferation of several non-hematopoietic cell types (osteoblasts, smooth muscle, endothelial and epithelial cells) [60].…”

Nestin+ Cells Isolated From The Peritoneum Attenuate Peritoneal Fibrosis Via Suppressing IL-33 /ST2 Signaling

“…However, these therapies cannot prevent PMC loss, which plays a critical role in causing PF [9]. Previous studies have suggested that PMCs showed strong labeling with antibodies against Nestin, which is a speci c marker for multifunctional, multilineage progenitor cells, indicating that these cells represent a "young", not entirely differentiated cell population [10]. The intermediate lament protein…”