Aims: 

Intraperitoneal injection of Freund's adjuvant induces acute peritonitis. As a result of this treatment large amount of macrophages and cells having numerous caveolae at their plasma membrane appeared in the peritoneal wash. Their morphology was different from the common macrophages, they were rather similar to mesothelial cells, but labelled with pan-macrophage antibodies. We studied whether mesothelial cells could transdifferentiate into macrophages.

Methods: 

1ml complete Freund adjuvant was injected into the peritoneal cavity to induce acute inflammation. The mesentery was prepared after 1, 2, 3, 5, 7 and 11 days of the injection. The samples were fixed in 4% paraformaldehyde (for immunohistochemistry), and 2% glutaraldehyde (for traditional light and electron microscopy), which was followed by washing and embedding into 12% gelatine. The epithelial/mesenchymal transition was studied by anti ED1 (pan-macrophage marker), anti-pan-cytokeratine (epithelial-specific intermedier filamentum), anti-mesothelin (mesothel marker) antibodies. Studying the possible role of caveolae/caveolin in this transdifferentiation we have used anti-caveolin-1 antibody as well.

Results: 

By the time of the adjuvant treatment the macrophage markers (ED1) expression increased in the mesothelial cells and more cells (double-labelled with anti-mesothelin and anti-ED1 antibodies) were found to be detached from the mesentery. Parallel to this the cytokeratine expression of the mesothelial cells has gradually decreased. At the 5th day of the inflammation practically there was no cytokeratine labelling present in the mesothelial cells and the mesothelin expression has significantly decreased. The plasma membrane caveolin-1 labelling has also changed: we found strong caveolin-1 labelling inside of the cytoplasm (perinuclear localization) indicating that inflammation resulted in the internalization of caveolae.

Conclusion: 

These results strongly suggest that mesothelial cells are not entirely differentiated, and represent a multipotential cell lineage. Under special stimuli these cells can leave the mesentery, undergo epithelial/mesenchymal transition and differentiate into phagocytotic (macrophage-like) cells. Signal transduction pathways are involved in this transdifferentiation process. Our results indicate that caveolae/caveolin can play important regulatory role in this signal transduction.