Homing and adhesion molecules in autoimmune gastritis.
The pathogenesis of autoimmune gastritis is the result of lymphocyte infiltration of the gastric mucosa, however, the events leading to the selective extravasation of autoreactive lymphocytes are unclear. Here we have examined the expression of adhesion molecules in the gastric mucosa of BALB/c mice with neonatal thymectomy-induced gastritis. The overall area of vascular endothelium was not significantly different between gastritic and non-gastritic mice. However, a significant increase in the area of mucosal endothelium expressing MAdCAM-1 in gastritic mice was observed. Treatment of neonatally thymectomized BALB/c mice with a MAdCAM-1 specific monoclonal antibody (MECA 367) reduced the incidence of autoimmune gastritis from 80 to 26%. Treatment with a monoclonal antibody (R1-2) directed to the MAdCAM-1 ligand, alpha4beta7, also resulted in a reduction in the incidence of gastritis to 40%. These findings identify the alpha4beta7/MAdCAM-I interaction as a pivotal event in the initiation of autoimmune gastritis.
Barrett
S P
SP
Department of Pathology and Immunology, Monash University Medical School, Prahran, Victoria, Australia. simon.barrett@med.monash.edu.au
Riordon
A
A
Toh
B H
BH
Gleeson
P A
PA
van Driel
I R
IR
D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015703:Antigens, CD / Q000378:metabolism; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D005756:Gastritis / Q000209:etiology / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control; D007074:Immunoglobulin G / Q000627:therapeutic use; D007136:Immunoglobulins / Q000276:immunology / Q000378:metabolism*; D039441:Integrin alpha4; D051379:Mice; D008807:Mice, Inbred BALB C; D009088:Mucoproteins / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D013934:Thymectomy / Q000009:adverse effects
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D007074:Immunoglobulin G; D007136:Immunoglobulins; C489082:Madcam1 protein, mouse; C504268:Madcam1 protein, rat; D009088:Mucoproteins; D039441:Integrin alpha4