Selective antibody blockade of lymphocyte migration to mucosal sites and mast cell adhesion.
The integrins alpha4beta7 and alpha4beta1 mediate adhesion to the mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and the vascular cell adhesion molecule-1 (VCAM-1) and are important in T cell and allergic inflammatory reactions in the rat. The relative contributions of alpha4beta7 and alpha4beta1 in these reactions is unknown. To examine the role of alpha4beta7 in the rat a new mAb, TA-6, was developed. TA-6 inhibited adhesion to MAdCAM-1 but not to VCAM-1, a characteristic of alpha4beta7 adhesion, and immunofluorescence and immunoprecipitation studies were compatible with binding to alpha4beta7. TA-6 blocked rat lymphocyte adhesion to mesenteric lymph nodes and T cell migration to mucosal lymphoid tissues and it bound to rat mucosal mast cells. TA-6 did not inhibit lymphocyte adhesion to peripheral lymph nodes and T cell migration to peripheral lymphoid tissues or cutaneous inflammatory sites, and was not expressed on connective tissue mast cells.
Palecanda
A
A
Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.
Marshall
J S
JS
Li
X
X
Briskin
M J
MJ
Issekutz
T B
TB
D000818:Animals; D019138:Antibodies, Blocking / Q000378:metabolism / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology*; D000937:Antigen-Antibody Reactions; D016466:CHO Cells; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules; D002465:Cell Movement / Q000276:immunology*; D003239:Connective Tissue Cells / Q000276:immunology / Q000378:metabolism; D006224:Cricetinae; D003872:Dermatitis / Q000276:immunology / Q000473:pathology; D007136:Immunoglobulins / Q000378:metabolism; D016023:Integrins / Q000096:biosynthesis / Q000276:immunology* / Q000502:physiology; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009088:Mucoproteins / Q000378:metabolism; D011233:Precipitin Tests; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D016023:Integrins; C489082:Madcam1 protein, mouse; C504268:Madcam1 protein, rat; D009088:Mucoproteins; D019010:Vascular Cell Adhesion Molecule-1; C071777:integrin alpha4beta7