Loss of CD34 leads to exacerbated autoimmune arthritis through increased vascular permeability.
CD34 is a cell surface sialomucin expressed by hematopoietic precursors, eosinophils, mast cells, and vascular endothelia and is suggested to play an integral role in mucosal inflammatory responses. Although Cd34(-/-) mice have normal hematopoietic cell subsets in peripheral tissues at steady state, they exhibit a cell recruitment defect when challenged, offering a unique opportunity to distinguish between local inflammatory cell proliferation and peripheral recruitment in disease. Autoimmune arthritis is an inflammatory disease dependent on hematopoietic infiltration, and in this study, we have examined the role of CD34 in disease development and progression. Using an autoimmune serum transfer model, arthritis was induced in C57BL/6 wild-type and Cd34(-/-) mice. Surprisingly, we found that Cd34(-/-) mice were more susceptible to arthritis than wild-type mice. We examined mast cell-transplanted, eosinophil-deficient, and bone marrow-chimeric mice to determine the role of CD34 expression on disease progression. These experiments excluded CD34-deficient mast cells, eosinophils, or hematopoietic cells as the cause of the exacerbated disease. Further study demonstrated that Cd34(-/-) mice exhibit increased vascular leakage at onset of disease and in response to TNF, which correlated with a subsequent increase in disease severity. We conclude that loss of CD34 expression leads to increased vascular permeability in the joints at onset of disease, leading to exacerbated arthritic disease in Cd34(-/-) mice.
Blanchet
Marie-Renée
MR
The Biomedical Research Center, University of British Columbia, Vancouver, British Columbia, Canada.
Gold
Matthew
M
Maltby
Steven
S
Bennett
Jami
J
Petri
Björn
B
Kubes
Paul
P
Lee
David M
DM
McNagny
Kelly M
KM
D000818:Animals; D018952:Antigens, CD34 / Q000235:genetics* / Q000502:physiology; D001169:Arthritis, Experimental / Q000235:genetics* / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000473:pathology; D002199:Capillary Permeability / Q000235:genetics* / Q000276:immunology*; D002478:Cells, Cultured; D018450:Disease Progression; D016130:Immunophenotyping; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D012720:Severity of Illness Index
D018952:Antigens, CD34