CD34 mediates intestinal inflammation in Salmonella-infected mice.
CD34 is a highly glycosylated sialomucin expressed on a variety of cells, ranging from vascular endothelial cells to haematopoietic stem cells. Depending on its glycosylation state, CD34 has been shown to promote or inhibit cell adhesion and migration; however, a functional role for CD34 in the gut has not been determined. Using a model of Salmonella-induced gastroenteritis, we investigated the role of CD34 in the context of infection. Upon oral infection, the number of CD34+ cells detected in the submucosa, vascular endothelium and lamina propria significantly increased in S. Typhimurium-infected C57Bl/6 mice. The pathology of S. Typhimurium-infected C57Bl/6 mice was characterized by recruitment of neutrophils to the site of inflammation, submucosal oedema and crypt destruction. In contrast, Cd34(-/-) mice showed a delayed pathology, a defect in inflammatory cell migration into the intestinal tissue and enhanced survival. Importantly, this was not due to a lack of chemotactic signals in Cd34(-/-) mice as these mice had either similar or significantly higher levels of pro-inflammatory cytokines and chemokines post infection when compared with infected C57/Bl6 control mice. In summary, we demonstrate a novel role for CD34 in enhancing migration of inflammatory cells and thereby exacerbating host-mediated immunopathology in the intestine of S. Typhimurium-infected mice.
Grassl
Guntram A
GA
Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Faustmann
Marco
M
Gill
Navkiran
N
Zbytnuik
Lori
L
Merkens
Helen
H
So
Leslie
L
Rossi
Fabio M
FM
McNagny
Kelly M
KM
Finlay
B Brett
BB
D000818:Animals; D018952:Antigens, CD34 / Q000276:immunology* / Q000378:metabolism; D002432:Cecum / Q000276:immunology* / Q000473:pathology*; D002448:Cell Adhesion; D002465:Cell Movement; D018925:Chemokines / Q000276:immunology; D004487:Edema; D004730:Endothelium, Vascular / Q000276:immunology; D005759:Gastroenteritis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D012481:Salmonella Infections, Animal / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D012486:Salmonella typhimurium
D018952:Antigens, CD34; D018925:Chemokines