Control of islet intercellular adhesion molecule-1 expression by interferon-alpha and hypoxia.
The ability of interferon-alpha (IFN-alpha) to induce the adhesion molecules that characterize the islets of patients with type I diabetes has been investigated. We have found that all tested recombinant IFN-as will induce major histocompatibility complex (MHC) class I on arterial endothelial cells. Some but not all IFN-as will induce intercellular adhesion molecule-1 (ICAM-1). However, there is only a transient and modest increase in VCAM on arterial endothelial cells. IFN-alpha has very little effect on endothelial MHC class II expression but will induce these proteins on monocytes. Thus, there is a close concordance between the biological actions of IFN-alpha and the appearance of those adhesion molecules induced in the islets of patients with type I diabetes. IFN-alpha is also produced in normal human islets during short-term cultures, probably as a result of the ischemia present at the center of the islet. This induction of IFN-alpha by hypoxia may explain the previously reported spontaneous induction of ICAM-1 in human islets and may also be a contributing factor to the failure of islet grafts.
Chakrabarti
D
D
Department of Molecular Oncology, Genentech, Inc., South San Francisco, California 94080, USA.
Huang
X
X
Beck
J
J
Henrich
J
J
McFarland
N
N
James
R F
RF
Stewart
T A
TA
D001158:Arteries; D015687:Cell Hypoxia; D002478:Cells, Cultured; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology*; D006681:HLA-D Antigens / Q000032:analysis / Q000096:biosynthesis*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects / Q000276:immunology*; D007700:Kinetics; D008285:Major Histocompatibility Complex / Q000187:drug effects; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014469:Umbilical Arteries
D017931:DNA Primers; D006681:HLA-D Antigens; D015395:Histocompatibility Antigens Class I; D007370:Interferon Type I; D015345:Oligonucleotide Probes; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma