Aberrant wound healing and TGF-beta production in the autoimmune-prone MRL/+ mouse.
Wound healing is a complex process that involves inflammation, apoptosis, growth, and tissue remodeling. The autoimmune-prone inbred mouse strain MRL/+ manifests accelerated and extensive healing to ear punch wounds, suggesting a link between immune defects and wound healing. Prior studies with lupus-prone mice have shown that hematopoietic cells of lupus-prone strains can transfer disease to otherwise non-autoimmune-prone recipients. In this study we performed reciprocal bone marrow transfers between MRL and the control strain B10.BR and found that radioresistant MRL/+ host cells, rather than hematopoietic cells, are required for the healing response. We have also made the novel observations that, compared to normal controls, MRL/+ hematopoietic cells overproduce TGF-beta1 and manifest impaired inflammatory responses to lipopolysaccharide challenge. These features suggest that the aberrant wound healing phenotype of MRL mice is independent of their propensity to develop autoimmunity.
Kench
J A
JA
Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado, 80206, USA.
Russell
D M
DM
Fadok
V A
VA
Young
S K
SK
Worthen
G S
GS
Jones-Carson
J
J
Henson
J E
JE
Henson
P M
PM
Nemazee
D
D
D000375:Aging / Q000235:genetics / Q000502:physiology; D000818:Animals; D016026:Bone Marrow Transplantation; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D005838:Genotype; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D019463:Mice, Inbred MRL lpr / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology; D011014:Pneumonia / Q000503:physiopathology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D018183:Transplantation Chimera; D014945:Wound Healing / Q000235:genetics / Q000502:physiology*
D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016212:Transforming Growth Factor beta