Importance of innate immunity and collagen binding integrin alpha1beta1 in TNBS-induced colitis.
Inflammation occurs in the context of integrin-mediated adhesive interactions of cells with their extracellular matrix environment. We investigated the role of the collagen binding integrin alpha1beta1 in a model of colitis. alpha1beta1 was expressed on lamina propria T cells and monocytes during disease. Both alpha1 deficiency and anti-alpha1 mAb treatment (prophylactic and therapeutic) protected against colitis. In vivo alpha1beta1 blockade improved macroscopic and histologic scores, decreased inflammatory cytokine production, and profoundly affected the ability of lamina propria mononuclear cells to proliferate and produce IFN-gamma in vitro. Development and alpha1-mediated inhibition of colitis can be lymphocyte independent, suggesting that activated monocytes also represent a key alpha1beta1-expressing cell type involved in colitis. These results underscore the importance of innate immunity and, specifically, of leukocyte/matrix interactions in regulating local inflammatory responses.
Fiorucci
Stefano
S
Clinica di Gastroenterologia ed Endoscopia Digestiva, Dipartimento di Medicina Clinica, Patologia Università di Perugia, Italy.
Mencarelli
Andrea
A
Palazzetti
Barbara
B
Sprague
Andrew G
AG
Distrutti
Eleonora
E
Morelli
Antonio
A
Novobrantseva
Tatiana I
TI
Cirino
Giuseppe
G
Koteliansky
Victor E
VE
de Fougerolles
Antonin R
AR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology*; D003094:Collagen / Q000276:immunology; D005109:Extracellular Matrix / Q000276:immunology; D005260:Female; D007113:Immunity, Innate; D039222:Integrin alpha1beta1 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009000:Monocytes / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
D000911:Antibodies, Monoclonal; D039222:Integrin alpha1beta1; D014302:Trinitrobenzenesulfonic Acid; D003094:Collagen