Abstract
During the inflammatory response, the adhesion molecule PECAM plays a crucial role in transendothelial migration, the passage of leukocytes across endothelium. We report here an additional role for PECAM in the subsequent migration of monocytes through the subendothelial extracellular matrix. PECAM has six immunoglobulin (Ig) superfamily domains. Monoclonal antibodies whose epitopes map to domains 1 and/or 2 selectively block monocyte migration through the endothelial junction, whereas those that map to domain 6 block only the migration through the extracellular matrix, trapping the monocyte between the endothelium and its basal lamina. Therefore, transendothelial migration (diapedesis) and passage through extracellular matrix (interstitial migration) are distinct and separable phases of monocyte emigration. Furthermore, distinct and separate Ig domains of PECAM are involved in mediating these two steps.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antibodies, Monoclonal / pharmacology
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Antigens, Differentiation, Myelomonocytic / chemistry
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Antigens, Differentiation, Myelomonocytic / genetics
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Antigens, Differentiation, Myelomonocytic / immunology
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Antigens, Differentiation, Myelomonocytic / physiology*
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Base Sequence
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Cell Adhesion
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Cell Adhesion Molecules / chemistry
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Cell Adhesion Molecules / genetics
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Cell Adhesion Molecules / immunology
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Cell Adhesion Molecules / physiology*
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Cell Movement
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Cells, Cultured
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Chlorocebus aethiops
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Endothelium, Vascular / cytology*
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Endothelium, Vascular / metabolism
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Extracellular Matrix / metabolism*
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Humans
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Immunoglobulin G / genetics
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Inflammation
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Molecular Sequence Data
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Monocytes / physiology*
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Platelet Endothelial Cell Adhesion Molecule-1
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Protein Structure, Tertiary
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Recombinant Fusion Proteins / immunology
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Recombinant Fusion Proteins / pharmacology
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Umbilical Veins
Substances
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Antibodies, Monoclonal
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Antigens, Differentiation, Myelomonocytic
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Cell Adhesion Molecules
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Immunoglobulin G
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Platelet Endothelial Cell Adhesion Molecule-1
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Recombinant Fusion Proteins