Abstract
RANTES (regulated on activation, normal T expressed and secreted) is a member of the chemotactic cytokine (chemokine) beta subfamily. High affinity receptors for RANTES have been identified on a human monocytic leukemia cell line THP-1, which responded to RANTES in chemotaxis and calcium mobilization assays. Steady-state binding data analyses revealed approximately 700 binding sites/cell on THP-1 cells with a Kd value of 400 pM, comparable to that expressed on human peripheral blood monocytes. The RANTES binding to monocytic cells was competed for by monocyte chemotactic and activating factor (MCAF) and macrophage inflammatory protein 1 (MIP-1) alpha, two other chemokine beta cytokines. Although MCAF and MIP-1 alpha competed for RANTES binding to monocytes with apparent lower affinity (with estimated Kd of 6 and 1.6, nM respectively) both of these cytokines effectively desensitized the calcium mobilization induced by RANTES. The chemotactic response of THP- 1 cells to RANTES was also markedly inhibited by preincubation with MCAF or MIP-1 alpha. In contrast, RANTES did not desensitize the THP-1 calcium mobilization and chemotaxis in response to MCAF or MIP-1 alpha. These results, together with our previous observations that RANTES did not compete for MCAF or MIP-1 alpha binding on monocytic cells, indicate the expression of promiscuous receptors on monocytes that recognize one or more cytokines within the chemokine beta family.
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- Holmes W. E., Lee J., Kuang W. J., Rice G. C., Wood W. I. Structure and functional expression of a human interleukin-8 receptor. Science. 1991 Sep 13;253(5025):1278–1280. doi: 10.1126/science.1840701. [DOI] [PubMed] [Google Scholar]
- Kameyoshi Y., Dörschner A., Mallet A. I., Christophers E., Schröder J. M. Cytokine RANTES released by thrombin-stimulated platelets is a potent attractant for human eosinophils. J Exp Med. 1992 Aug 1;176(2):587–592. doi: 10.1084/jem.176.2.587. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kuna P., Reddigari S. R., Schall T. J., Rucinski D., Viksman M. Y., Kaplan A. P. RANTES, a monocyte and T lymphocyte chemotactic cytokine releases histamine from human basophils. J Immunol. 1992 Jul 15;149(2):636–642. [PubMed] [Google Scholar]
- Lee J., Horuk R., Rice G. C., Bennett G. L., Camerato T., Wood W. I. Characterization of two high affinity human interleukin-8 receptors. J Biol Chem. 1992 Aug 15;267(23):16283–16287. [PubMed] [Google Scholar]
- Moser B., Schumacher C., von Tscharner V., Clark-Lewis I., Baggiolini M. Neutrophil-activating peptide 2 and gro/melanoma growth-stimulatory activity interact with neutrophil-activating peptide 1/interleukin 8 receptors on human neutrophils. J Biol Chem. 1991 Jun 5;266(16):10666–10671. [PubMed] [Google Scholar]
- Oh K. O., Zhou Z., Kim K. K., Samanta H., Fraser M., Kim Y. J., Broxmeyer H. E., Kwon B. S. Identification of cell surface receptors for murine macrophage inflammatory protein-1 alpha. J Immunol. 1991 Nov 1;147(9):2978–2983. [PubMed] [Google Scholar]
- Samanta A. K., Oppenheim J. J., Matsushima K. Identification and characterization of specific receptors for monocyte-derived neutrophil chemotactic factor (MDNCF) on human neutrophils. J Exp Med. 1989 Mar 1;169(3):1185–1189. doi: 10.1084/jem.169.3.1185. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schall T. J., Bacon K., Toy K. J., Goeddel D. V. Selective attraction of monocytes and T lymphocytes of the memory phenotype by cytokine RANTES. Nature. 1990 Oct 18;347(6294):669–671. doi: 10.1038/347669a0. [DOI] [PubMed] [Google Scholar]
- Schall T. J. Biology of the RANTES/SIS cytokine family. Cytokine. 1991 May;3(3):165–183. doi: 10.1016/1043-4666(91)90013-4. [DOI] [PubMed] [Google Scholar]
- Schall T. J., Jongstra J., Dyer B. J., Jorgensen J., Clayberger C., Davis M. M., Krensky A. M. A human T cell-specific molecule is a member of a new gene family. J Immunol. 1988 Aug 1;141(3):1018–1025. [PubMed] [Google Scholar]
- Tsuchiya S., Yamabe M., Yamaguchi Y., Kobayashi Y., Konno T., Tada K. Establishment and characterization of a human acute monocytic leukemia cell line (THP-1). Int J Cancer. 1980 Aug;26(2):171–176. doi: 10.1002/ijc.2910260208. [DOI] [PubMed] [Google Scholar]
- Walz A., Dewald B., von Tscharner V., Baggiolini M. Effects of the neutrophil-activating peptide NAP-2, platelet basic protein, connective tissue-activating peptide III and platelet factor 4 on human neutrophils. J Exp Med. 1989 Nov 1;170(5):1745–1750. doi: 10.1084/jem.170.5.1745. [DOI] [PMC free article] [PubMed] [Google Scholar]