GM-CSF and GM-CSF receptor have regulatory role in transforming rat mesenteric mesothelial cells into macrophage-like cells

Abstract

Objective and design: During peritonitis, mesothelial cells assume macrophage characteristics, expressing macrophage markers, indicating that they might differentiate into macrophage-like cells.

Materials and subjects: Twenty-five male rats were used for in vivo experiments. For in vitro experiments, a primary mesentery culture model was developed. The mesothelial cell to macrophage-like cell transition was followed by studying ED1 expression.

Treatments: In vitro primary mesenteric culture was treated with granulocyte-macrophage colony-stimulating factor (GM-CSF, 1 ng/ml). Blocking internalization of receptor-ligand complex, Dynasore (80 µM) was used. Acute peritonitis was induced by Freund's adjuvant's (1 ml) intraperitoneal injection.

Results: Immunohistochemistry: GM-CSF in vitro treatment resulted in a prominent ED1 expression in transformed mesothelial cells. Blocking the internalization, ED1 expression could not be detected. GM-CSF receptor (both α and β) was expressed in mesothelial cells in vitro (even if the GM-CSF was not present) and in vivo. Inflammation resulted in an increasing GM-CSF and GM-CSF-receptor level in the lysate of mesothelial cells.

Conclusions: Mesothelial cells can differentiate into macrophage-like cells, and GM-CSF, produced by the mesothelial cells, has probably an autocrine regulatory role in this transition. Our results provide new data about the plasticity of mesothelial cell and support the idea that during inflammation macrophages can derive from non-hematopoietic sources as well.

Keywords: GM-CSF; Mesothelial cell transformation; Peritoneal macrophages; Peritonitis.