Regulation of dextran sodium sulfate induced colitis by leukocyte beta 2 integrins.
Inflammatory bowel diseases (IBD) are chronic inflammatory disorders whose etiology remains unknown. Reports have shown that infiltration of leukocytes into intestinal tissue is a pathognomonic hallmark for this disease. Leukocyte beta(2) integrins are heterodimeric adhesion membrane proteins that are exclusively expressed on leukocytes and participate in immune cell adhesion and activation. In this study, we examined the pathophysiological role of the beta(2) integrins CD18, CD11a, and CD11b in the pathogenesis of dextran sodium sulfte (DSS)-induced experimental colitis. Disease activity was measured by daily assessment of clinical parameters including stool consistency, weight loss, occult blood, and gross rectal bleeding. Histopathological changes including severity of inflammation, surface epithelial/crypt damage, and depth of injury were also determined. The CD18 null and CD11a null mice had significantly lower disease activity and cumulative histopathological scores compared to wild-type mice. Interestingly, CD11b null mice did not show protection against DSS colitis and displayed increased disease activity compared to wild-type mice. Examination of specific leukocyte populations in the distal colon from various mice revealed significant attenuation of neutrophil and macrophage infiltrates in CD18, CD11a, and CD11b null mice. Surprisingly, the CD11b null mice showed a significant increase in plasma cell infiltration in response to DSS suggesting that this molecule may influence plasma cell function during colitis. This study demonstrates that genetic loss of CD18 or CD11a is protective during experimental colitis and that CD11b may serve a regulatory role during development of disease.
Department of Pathology, LSU Health Sciences Center-Shreveport, Shreveport, LA 71130, USA.
Maisoun
M
Abdelbaqi
John H
JH
Chidlow
Kametra M
KM
Matthews
Kevin P
KP
Pavlick
Shayne C
SC
Barlow
Andrea J
AJ
Linscott
Matthew B
MB
Grisham
Marjorie R
MR
Fowler
Christopher G
CG
Kevil
D000818:Animals; D018988:Bacterial Translocation; D040881:CD11a Antigen / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D003106:Colon / Q000473:pathology; D016264:Dextran Sulfate; D016023:Integrins / Q000378:metabolism / Q000502:physiology*; D007962:Leukocytes / Q000378:metabolism / Q000502:physiology; D008264:Macrophages / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D040881:CD11a Antigen; D039481:CD11b Antigen; D018821:CD18 Antigens; D016023:Integrins; D016264:Dextran Sulfate