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Analysis of Physiologic E-Selectin-Mediated Leukocyte Rolling on Microvascular Endothelium
Published on: February 11, 2009
L-selectin-mediated lymphocyte rolling on MAdCAM-1
E L Berg1, L M McEvoy, C Berlin
1Department of Pathology, Stanford University, California 94305.
Nature
|December 16, 1993
Summary
Mucosal vascular addressin MAdCAM-1 is a facultative ligand for L-selectin, supporting lymphocyte rolling on mucosal vessels. This interaction is crucial for lymphocyte homing and immune surveillance in mucosal tissues.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- L-selectin is a C-type lectin crucial for lymphocyte trafficking to lymph nodes and Peyer's patches.
- It also mediates leukocyte interactions with inflamed venules, a key process in immune cell recruitment.
- Understanding lymphocyte homing mechanisms is vital for developing targeted therapies for inflammatory and autoimmune diseases.
Purpose of the Study:
- To investigate whether mucosal vascular addressin MAdCAM-1 serves as a ligand for L-selectin.
- To characterize the binding properties of MAdCAM-1 and its role in lymphocyte adhesion under shear conditions.
- To elucidate the dual role of MAdCAM-1 in supporting both selectin- and integrin-mediated lymphocyte interactions.
Main Methods:
- Isolation of MAdCAM-1 from mesenteric lymph nodes and cultured endothelioma cells.
- Functional adhesion assays using L-selectin-transfected lymphoid cells under shear stress.
- Analysis of carbohydrate structures on MAdCAM-1, including sialic acid content and N-glycanase resistance.
- Investigation of MAdCAM-1 as a ligand for the alpha 4 beta 7 integrin.
Main Results:
- Mucosal vascular addressin MAdCAM-1 was identified as a facultative ligand for L-selectin.
- MAdCAM-1 from mesenteric lymph nodes, but not from cultured cells, supported L-selectin-mediated lymphocyte adhesion under shear.
- This adhesion involved N-glycanase-resistant, sialic acid-containing carbohydrates on MAdCAM-1.
- Lymphoid cells exhibited rolling behavior on MAdCAM-1, mimicking selectin-dependent rolling in inflamed venules.
- MAdCAM-1 also functions as a ligand for the alpha 4 beta 7 integrin.
Conclusions:
- MAdCAM-1 is a key adhesion molecule involved in lymphocyte homing to mucosal tissues.
- It supports selectin-mediated lymphocyte rolling and integrin-mediated adhesion, facilitating lymphocyte arrest in vivo.
- MAdCAM-1's unique properties are critical for immune cell surveillance at mucosal sites.
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