Regulation of monocyte migration by amphoterin (HMGB1).
Amphoterin (HMGB1) is a 30-kD heparin-binding protein involved in process extension and migration of cells by a mechanism involving the receptor for advanced glycation end products (RAGE). High levels of amphoterin are released to serum during septic shock. We have studied the expression of amphoterin in monocytes and the role of amphoterin and RAGE in monocyte transendothelial migration. Un-activated monocytes in suspension did not reveal amphoterin on their surface, but adherent monocytes exported amphoterin to the cell surface. Immunohistochemical staining of arterial thrombi in vivo revealed amphoterin in mononuclear cells and in surrounding extracellular matrix. Amphoterin was secreted from phorbol ester and interferon-gamma (IFN-gamma)-activated macrophages, and the secretion was inhibited by blocking the adenosine 5'-triphosphate (ATP)-binding cassette transporter-1, a member of the multidrug resistance protein family. Amphoterin was specifically adhesive for monocytes in peripheral blood leukocyte adhesion assay. Adhesion caused an extensive spreading of cells, which was inhibited by the dominant-negative RAGE receptor (soluble ectodomain of RAGE), and adhesion up-regulated chromogranin expression in monocytes, also suggesting a RAGE-dependent interaction. Monocyte transendothelial migration was efficiently inhibited by anti-amphoterin and anti-RAGE antibodies and by the soluble RAGE. We suggest that amphoterin is an autocrine/paracrine regulator of monocyte invasion through the endothelium.
Rouhiainen
Ari
A
Neuroscience Center, Viikinkaari 4, PO Box 56, University of Helsinki, Helsinki 00014, Finland. ari.rouhiainen@helsinki.fi
Kuja-Panula
Juha
J
Wilkman
Erika
E
Pakkanen
Jukka
J
Stenfors
Jan
J
Tuominen
Raimo K
RK
Lepäntalo
Mauri
M
Carpén
Olli
O
Parkkinen
Jaakko
J
Rauvala
Heikki
H
D000818:Animals; D001773:Blood Cells; D001921:Brain / Q000166:cytology; D002448:Cell Adhesion; D002450:Cell Communication; D002460:Cell Line; D048430:Cell Shape; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D004730:Endothelium, Vascular / Q000378:metabolism; D017127:Glycation End Products, Advanced; D024243:HMGB1 Protein / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D021381:Protein Transport; D051381:Rats; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000502:physiology; D013927:Thrombosis / Q000473:pathology
D017127:Glycation End Products, Advanced; D024243:HMGB1 Protein; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic