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(American Journal of Pathology. 2002;160:681-692.)
© 2002 American Society for Investigative Pathology

Regular Articles

Stimulation of Mesothelial Cell Proliferation by Exudate Macrophages Enhances Serosal Wound Healing in a Murine Model

Steven E. Mutsaers*, Darrel Whitaker{dagger} and John M. Papadimitriou*

From the Department of Pathology,*
University of WesternAustralia, Perth; and the Department of AnatomicalPathology,{dagger}
The Western Australian Centre forPathology and Medical Research, QEII Medical Centre, Nedlands,Western Australia

Examination of thermally induced serosal lesions in mice displayed collections of inflammatory cells, predominantly macrophages, on and surrounding the wound within 48 hours of injury. Furthermore, by 2 days a large number of uninjured mesothelial cells adjacent to the wound were synthesizing DNA. From these findings, it was hypothesized that macrophages play a major role in serosal repair by stimulating mesothelial cell proliferation. Again, using a murine model of mesothelial regeneration, depletion of circulating monocytes significantly delayed serosal healing whereas addition of peritoneal exudate cells to the wound site 36 hours before injury increased the healing rate. In vivo assessment of mesothelial cell proliferation using tritiated thymidine incorporation and autoradiography demonstrated that peritoneal exudate cells stimulated mesothelial cell proliferation (12.44 ± 1.63% labeling index, compared with controls in which medium only was used 4.48 ± 0.71%). The mesothelial proliferation was predominantly because of macrophage-secreted products with molecular weights of 36 to 53 kd or 67 to 100 kd. These data support the hypothesis that macrophages play an important role in serosal healing by stimulating mesothelial cell proliferation.




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