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Your search keyword '"Tidswell M"' showing total 3 results
Start Over Author "Tidswell M" Topic receptors, lymphocyte homing
3 results on '"Tidswell M"'

1. Structure-function analysis of the integrin beta 7 subunit: identification of domains involved in adhesion to MAdCAM-1.

Author

Tidswell M, Pachynski R, Wu SW, Qiu SQ, Dunham E, Cochran N, Briskin MJ, Kilshaw PJ, Lazarovits AI, Andrew DP, Butcher EC, Yednock TA, and Erle DJ

Subjects
Animals, Antibodies, Monoclonal chemistry, Antibodies, Monoclonal genetics, Antibodies, Monoclonal physiology, Cations, Cell Adhesion Molecules, Epitope Mapping, Humans, Immunoglobulins immunology, Integrins genetics, Integrins immunology, Leukemia, Erythroblastic, Acute metabolism, Ligands, Mice, Molecular Sequence Data, Mucoproteins immunology, Protein Binding immunology, Rats, Recombinant Fusion Proteins chemistry, Serine immunology, Serine physiology, Structure-Activity Relationship, Transfection immunology, Tumor Cells, Cultured, Immunoglobulins metabolism, Integrin beta Chains, Integrins chemistry, Integrins physiology, Mucoproteins metabolism, Protein Structure, Tertiary, Receptors, Lymphocyte Homing metabolism
Abstract

Beta 7 integrins serve special roles in mucosal immunity. Alpha 4 beta 7-mediated adhesion to mucosal addressin cell adhesion molecule-1 (MAdCAM-1) directs lymphocyte homing to the gut, and alpha E beta 7 mediates binding of lymphocytes to E-cadherin on epithelial cells. Since alpha 4 beta 7 mediates adhesion to MAdCAM-1 but alpha 4 beta 1 does not, we used beta 7/beta 1 chimeras to directly assess the importance of specific regions of beta 7 in MAdCAM-1 binding. We found a region of beta 7 (residues 46-386) that accounts for specificity of alpha 4 beta 7 binding to MAdCAM-1. We also used human/mouse and human/rat chimeric beta 7 subunits to map epitopes recognized by fifteen anti-beta 7 mAbs. Six of seven Abs that block adhesion to MAdCAM-1 and E-cadherin (Fib 21, 22, 27, 30, 504; Act-1) mapped to amino acid residues 176-250. Residues 176-250 lie within the region of beta 7 that specifies MAdCAM-1 binding and also within a region that has a predicted structure homologous to the metal ion-dependent adhesion site (MIDAS) domains of the integrin subunits alpha L and alpha M. Three new Abs that recognize beta 7 in the presence of Mn2+, but not Ca2+, and promote adhesion to MAdCAM-1, mapped to amino acids 46-149. One blocking and five other Abs mapped to other regions (amino acids 387-725). We conclude that a MIDAS-like domain serves a critical role in beta 7 integrin-mediated adhesion.

Published
1997

2. Expression and function of the MAdCAM-1 receptor, integrin alpha 4 beta 7, on human leukocytes.

Author

Erle DJ, Briskin MJ, Butcher EC, Garcia-Pardo A, Lazarovits AI, and Tidswell M

Subjects
Adult, Animals, Cell Adhesion, Cell Adhesion Molecules, Cell Line, Humans, Integrin beta1, Integrins analysis, Leukocyte Common Antigens analysis, Manganese pharmacology, Mice, Immunoglobulins physiology, Integrins physiology, Lymphocytes physiology, Mucoproteins physiology, Receptors, Lymphocyte Homing physiology
Abstract

Recirculation of mouse lymphocytes to the gut involves binding of the lymphocyte integrin alpha 4 beta 7 to the mucosal vascular addressin, MAdCAM-1. In humans, indirect evidence suggests that CD4+ T cells that express high levels of alpha 4 beta 7 migrate selectively to the gut. We now report that human adult blood CD8+ T cells and B cells, like CD4+ T cells, have heterogeneous expression of alpha 4 beta 7. In contrast, NK cells, eosinophils, and newborn blood T and B cells have relatively homogeneous expression of alpha 4 beta 7. CD4+ and CD8+ T cell expression of alpha 4 beta 7 was related to age, CD45RA expression, and integrin beta 1 (CD29) expression, suggesting that alpha 4 beta 7 expression changes after primary activation of CD4+ and CD8+ T cells in vivo. To directly determine whether human alpha 4 beta 7 mediates adhesion to MAdCAM-1, we performed in vitro adhesion assays with two alpha 4 beta 7+ human lymphoma cell lines. The results indicate that human alpha 4 beta 7 is a receptor for MAdCAM-1, whereas alpha 4 beta 1 is not. Adhesion of HUT 78 cells to MAdCAM-1 required Mn2+, whereas adhesion of RPMI 8866 cells did not, suggesting that alpha 4 beta 7 may have at least two distinct functional states. The ability of lymphocytes to bind to MAdCAM-1 and recirculate to mucosal organs is likely to be influenced both by the level of alpha 4 beta 7 expression and by the functional state of the alpha 4 beta 7 molecule.

Published
1994

3. Expression and function of the MAdCAM-1 receptor, integrin alpha 4 beta 7, on human leukocytes

Author

David Erle, Mj, Briskin, Ec, Butcher, Garcia-Pardo A, Ai, Lazarovits, and Tidswell M

Subjects
Adult, Integrins, Manganese, Integrin beta1, Receptors, Lymphocyte Homing, Immunoglobulins, Cell Line, Mice, Mucoproteins, Cell Adhesion, Animals, Humans, Leukocyte Common Antigens, Lymphocytes, Cell Adhesion Molecules
Abstract

Recirculation of mouse lymphocytes to the gut involves binding of the lymphocyte integrin alpha 4 beta 7 to the mucosal vascular addressin, MAdCAM-1. In humans, indirect evidence suggests that CD4+ T cells that express high levels of alpha 4 beta 7 migrate selectively to the gut. We now report that human adult blood CD8+ T cells and B cells, like CD4+ T cells, have heterogeneous expression of alpha 4 beta 7. In contrast, NK cells, eosinophils, and newborn blood T and B cells have relatively homogeneous expression of alpha 4 beta 7. CD4+ and CD8+ T cell expression of alpha 4 beta 7 was related to age, CD45RA expression, and integrin beta 1 (CD29) expression, suggesting that alpha 4 beta 7 expression changes after primary activation of CD4+ and CD8+ T cells in vivo. To directly determine whether human alpha 4 beta 7 mediates adhesion to MAdCAM-1, we performed in vitro adhesion assays with two alpha 4 beta 7+ human lymphoma cell lines. The results indicate that human alpha 4 beta 7 is a receptor for MAdCAM-1, whereas alpha 4 beta 1 is not. Adhesion of HUT 78 cells to MAdCAM-1 required Mn2+, whereas adhesion of RPMI 8866 cells did not, suggesting that alpha 4 beta 7 may have at least two distinct functional states. The ability of lymphocytes to bind to MAdCAM-1 and recirculate to mucosal organs is likely to be influenced both by the level of alpha 4 beta 7 expression and by the functional state of the alpha 4 beta 7 molecule.

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