T cell adherence and mucosal injury in ulcerative colitis: involvement of integrin-fibronectin interaction in situ.
The mechanism whereby mononuclear cells, including T lymphocytes, accumulate in the mucosal lesions of patients with ulcerative colitis (UC) is unknown. Although the role played by vascular adhesion molecules in the abnormal recruitment of leukocytes has been emphasized, it does appear that fibronectin (FN), an extracellular matrix (ECM) protein, can play an important role in the persistence of active inflammation because of its effects on the proliferation, differentiation, and migration of cells. beta 1-integrins (VLA proteins) mediate cell adhesion to ECM proteins such as fibronectin, laminin, and collagen. Peripheral blood T lymphocytes (PBL-T) showed increased expression of VLA proteins after activation, although the expression of VLA proteins by lamina propria lymphocytes (LPL) is not known. In an in-vitro binding assay, PBL-T showed increased adherence to inflamed mucosa from patients with UC after stimulation with CD3 crosslinking. This adherence was partially inhibited by antibodies specific for plasma FN, VLA-4, VLA-5, and VLA-beta 1, and by the synthetic peptide RGDS. These findings suggest that infiltrating T cells derived from blood use FN receptors to anchor at inflammatory sites. It is conceivable that the inhibition of T cell adherence to ECM by antibodies or synthetic peptides could suppress inflammatory activity in UC.
Ito
M
M
Department of Pathology, School of Medicine, Yamagata University, Japan.
Hirata
S
S
Arai
S
S
Takahashi
T
T
D015815:Cell Adhesion Molecules / Q000276:immunology*; D003093:Colitis, Ulcerative / Q000276:immunology*; D003106:Colon / Q000276:immunology; D005353:Fibronectins / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology; D017469:Receptors, Fibronectin / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D015815:Cell Adhesion Molecules; D005353:Fibronectins; D016023:Integrins; D017469:Receptors, Fibronectin