Human mononuclear phagocytes express the insulin-like growth factor-II/mannose-6-phosphate receptor.
The insulin-like growth factor (IGF)-II/mannose-6-phosphate (M6P) receptor, which targets acid hydrolases to lysosomes, is a multifunctional protein with separate binding sites for IGF-II and M6P. The purpose of this study was to determine if alveolar macrophages (AM) and their precursor cells, blood monocytes, expressed this receptor. AM expressed IGF-II/M6P receptors as detected by [125]IGF-II surface binding that was not reduced by recombinant IGF-I or IGF-I receptor monoclonal antibody (alpha IR3). Surface binding was also detected on blood monocytes and could be upregulated approximately 4-fold by incubation with lipopolysaccharide. There were no differences in surface binding by AM lavaged from individuals with asbestos exposure or from normal volunteers. Using the polymerase chain reaction and reverse transcriptase to reverse-transcribe mRNA from mononuclear phagocytes, specific IGF-II/M6P receptor cDNA was amplified and detected by agarose gel electrophoresis from both AM and blood monocytes. The IGF-II/M6P receptor has an intracellular transport role in many cells cycling from the cell surface to the cytoplasm, or binding to phosphorylated acid hydrolases in the Golgi and transporting them to an acidic prelysosomal site where they dissociate and fuse to the lysosomes and IGF-II/M6P recycles to the trans-Golgi. These functions may be particularly important in asbestosis and other interstitial lung diseases where AM are activated, intracellular lysosomes are a prominent morphologic feature, and acid hydrolases are found in recovered lavage fluid.
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Department of Medicine, Bellevue Hospital, New York University Medical Center, New York 10016.
D001194:Asbestos / Q000009:adverse effects; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004247:DNA / Q000235:genetics; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008875:Middle Aged; D008969:Molecular Sequence Data; D010586:Phagocytes / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011650:Pulmonary Alveoli / Q000166:cytology; D012333:RNA, Messenger / Q000235:genetics; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D017451:Receptors, Somatomedin
D012333:RNA, Messenger; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D001194:Asbestos; D007335:Insulin-Like Growth Factor II; D004247:DNA