Development of peritoneal adhesions in macrophage depleted mice.
BACKGROUND
We present a new mouse model for the study of peritoneal adhesions using macrophage Fas-induced apoptosis (Mafia) transgenic mice expressing a Fas-FKBP construct under control of the murine c-fms promoter. Mafia mice allow systemic macrophage depletion by dimerization of Fas with a synthetic dimerizer, AP20187. Results demonstrate that macrophage depletion in Mafia mice induces peritoneal adhesion formation when the peritoneal cavity is also exposed to an irritant. The Mafia mouse model presents a reproducible, non-surgical approach for research in adhesion formation and prevention.


METHODS
Mafia mice were treated with AP20187 using an intravenous (i.v.) or intraperitoneal (i.p.) injection. Control groups included mock-treated Mafia mice and both AP20187 and mock-treated wild type mice. Seven days after treatment, mice were observed for the presence of adhesions.


RESULTS
After i.p. injection with AP20187, 76% of Mafia mice developed adhesions whereas none of the mock-treated Mafia or wild-type mice developed adhesions, and only one AP20187-treated wild-type mouse (5.8%) developed a mild adhesion. Mafia mice treated with AP20187 i.v. exhibited macrophage depletion not significantly different than i.p. treated mice, but did not develop adhesions. In contrast, Mafia mice treated with AP20187 i.v. developed adhesions when diluent was also injected into the peritoneal cavity, whereas i.p diluent alone had no effect.


CONCLUSIONS
Macrophage depletion, combined with a peritoneal irritant, results in peritoneal adhesion formation in transgenic Mafia mice. Macrophages appear to play a protective role in the development and/or repair of peritoneal adhesions.
Burnett
Sandra H
SH
Department of Microbiology and Molecular Biology, Brigham Young University, Provo, Utah 84602, USA.
Beus
Bo J
BJ
Avdiushko
Rita
R
Qualls
Joseph
J
Kaplan
Alan M
AM
Cohen
Don A
DA
D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D053222:Fas Ligand Protein; D016236:Genes, fms; D008264:Macrophages; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010532:Peritoneal Diseases / Q000276:immunology* / Q000662:veterinary; D016559:Tacrolimus / Q000031:analogs & derivatives* / Q000494:pharmacology; D000267:Tissue Adhesions; D048069:Tumor Necrosis Factors
C463061:AP20187; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D048069:Tumor Necrosis Factors; D016559:Tacrolimus