Abstract
Monocytes are the predominant inflammatory cell recruited to xenografts and participate in delayed xenograft rejection. In contrast to allogeneic leukocytes that require up-regulation of endothelial adhesion molecules to adhere and emigrate into effector tissues, we demonstrate that human monocytes adhere rapidly to unstimulated xenogeneic endothelial cells. The major xenoantigen galactosealpha(1,3)galactosebeta(1,4)GlcNAc-R (alpha-gal) is abundantly expressed on xenogeneic endothelium. We have identified a putative receptor for alpha-gal on human monocytes that is a member of the C-type family of lectin receptors. Monocyte arrest under physiological flow conditions is regulated by alpha-gal, because cleavage or blockade results in a dramatic reduction in monocyte adhesion. Recruitment of human monocytes to unactivated xenogeneic endothelial cells requires both alpha(4) and beta(2) integrins on the monocyte; binding of alpha-gal to monocytes results in rapid activation of beta(2), but not alpha(4), integrins. Thus, activation of monocyte beta(2) integrins by alpha-gal expressed on xenogeneic endothelium provides a mechanism that may explain the dramatic accumulation of monocytes in vivo.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD / metabolism
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Antigens, Heterophile / metabolism
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Antigens, Heterophile / physiology*
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CD18 Antigens / physiology
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Cell Adhesion / immunology
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Cell Adhesion Molecules / metabolism
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Cell Movement / immunology
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Cells, Cultured
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Disaccharides / biosynthesis
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Disaccharides / metabolism
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Disaccharides / physiology*
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Endothelium, Vascular / cytology*
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Endothelium, Vascular / immunology*
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Endothelium, Vascular / metabolism
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Epitopes / metabolism
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Epitopes / physiology*
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Humans
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Integrin alpha4 / physiology
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Intercellular Adhesion Molecule-1 / metabolism
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K562 Cells
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L-Selectin / physiology
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Lectins, C-Type / metabolism
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Lectins, C-Type / physiology*
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Ligands
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Monocytes / metabolism
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Monocytes / physiology*
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Protein Binding / immunology
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Rheology / methods
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Swine
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Trisaccharides / biosynthesis
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Trisaccharides / metabolism
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Trisaccharides / physiology*
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U937 Cells
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Vascular Cell Adhesion Molecule-1 / metabolism
Substances
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Antigens, CD
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Antigens, Heterophile
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CD18 Antigens
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Cell Adhesion Molecules
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Disaccharides
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Epitopes
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ICAM2 protein, human
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Lectins, C-Type
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Ligands
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Trisaccharides
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Vascular Cell Adhesion Molecule-1
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alpha-galactosyl epitope
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Intercellular Adhesion Molecule-1
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L-Selectin
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galactosyl-(1-3)galactose
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Integrin alpha4