title: Chemoattractant receptors for interleukin-8 and C5a: expression on peripheral blood leukocytes and differential regulation on HL-60 and AML-193 cells by vitamin D3 and all-trans retinoic acid.
abstract: Two homologous high-affinity receptors for the chemoattractant interleukin-8, IL-8RA and IL-8RB, and one for the chemoattractant C5a (C5aR) have been cloned. These membrane proteins are members of the rhodopsin superfamily of G-protein coupled seven-transmembrane segment receptors. New monoclonal antibodies (mAb) directed against the deduced N-terminal sequences of the IL-8RA (mAb SE2) and IL-8RB (mAb HC2) were generated to determine the IL-8R expression on human blood leukocytes and two human myeloid cell lines. The C5aR expression was detected using the mAb W17/1. Approximately 107,000 C5aR, 55,000 IL-8RA, and 25,000 IL-8RB molecules per cell could be detected on human granulocytes by flow cytometric analysis. On peripheral blood monocytes, 42,000 C5aR molecules/cell and 3000 IL-8RB molecules/cell were expressed. However, we were unable to quantitate IL-8RA expression, which was detectable but below 2500 molecules per cell and thus outside the standard range for the quantitation of receptor molecules by flow cytometry. On AML-193 cells, only the IL-8RB was constitutively expressed, whereas on HL-60 cells, we could not detect expression of any of the three receptors. Vitamin D3 (250 ng/ml, 7 days), which has been shown to induce differentiation of AML-193 and HL-60 cells into the monocytic phenotype, led to an up-regulation of IL-8RB and C5aR in both cell lines in the absence of any expression of IL-8RA. In contrast, all-trans retinoic acid (0.1 microM, 7 days), which induces differentiation into the granulocytic phenotype, led to an up-regulation of IL-8RB in AML-193 cells and to an expression of IL-8RB and C5aR in HL-60 cells. Again, neither cell line expressed IL-8RA. These findings suggest that regulation of IL-8RA expression differs from that of its IL-8RB homolog and may be a late event in leukocyte maturation.
authors.affiliation: Department of Immunology, Georg-August University of Göttingen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Zahn
authors.forename: J
authors.initials: J
authors.lastname: Zwirner
authors.forename: H P
authors.initials: HP
authors.lastname: Spengler
authors.forename: O
authors.initials: O
authors.lastname: Götze
mesh_terms: D015703:Antigens, CD / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002630:Chemotactic Factors / Q000378:metabolism*; D002762:Cholecalciferol / Q000494:pharmacology*; D015936:Complement C5a / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute; D007962:Leukocytes / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D023062:Receptors, Interleukin-8A; D014212:Tretinoin / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000633:toxicity
chemical_list: D015703:Antigens, CD; D002630:Chemotactic Factors; D016209:Interleukin-8; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A; D010566:Virulence Factors, Bordetella; D002762:Cholecalciferol; D014212:Tretinoin; D015936:Complement C5a; D019204:GTP-Binding Proteins