Abstract
Equilibrium binding studies with recombinant human chemoattractant cytokines Rantes and monocyte chemoattractant protein 1 (MCP-1) on monocytic THP-1 cells have allowed the functional identification of two distinct receptors for C-C chemokines. One is a novel oligospecific receptor with high affinity for Rantes (50% maximal inhibitory concentration [IC50], 0.68 nM) and low affinity (IC50, 35 nM) for MCP- 1, while the other is the previously described specific receptor for MCP-1 (IC50, 0.5 nM). Receptor affinity for Rantes is enhanced on preparation of isolated membranes with a 12-fold decrease in receptor Kd. The basis of this enhancement is not understood. The Rantes receptor appears to be G protein linked, as binding activity is abolished by guanosine 5'-O-(3-thiotriphosphate) (IC50, 7.3 nM). In contrast to the consequences of MCP-1 binding, we were unable to demonstrate ligand-dependent calcium fluxes on binding of Rantes to human monocytes or THP-1 cells. The binding of Rantes and MCP-1 to mononuclear cells from dog, rabbit, and rat were tested. While high affinity binding could be demonstrated in dog and rabbit, differences in ligand-induced Ca2+ fluxes could be shown between species. This suggests that receptor-ligand interactions and receptor coupling is best examined with autologous receptors and cytokine.
Full Text
The Full Text of this article is available as a PDF (497.7 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alam R., Lett-Brown M. A., Forsythe P. A., Anderson-Walters D. J., Kenamore C., Kormos C., Grant J. A. Monocyte chemotactic and activating factor is a potent histamine-releasing factor for basophils. J Clin Invest. 1992 Mar;89(3):723–728. doi: 10.1172/JCI115648. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bischoff S. C., Krieger M., Brunner T., Dahinden C. A. Monocyte chemotactic protein 1 is a potent activator of human basophils. J Exp Med. 1992 May 1;175(5):1271–1275. doi: 10.1084/jem.175.5.1271. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Butcher E. C. Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell. 1991 Dec 20;67(6):1033–1036. doi: 10.1016/0092-8674(91)90279-8. [DOI] [PubMed] [Google Scholar]
- Cushing S. D., Berliner J. A., Valente A. J., Territo M. C., Navab M., Parhami F., Gerrity R., Schwartz C. J., Fogelman A. M. Minimally modified low density lipoprotein induces monocyte chemotactic protein 1 in human endothelial cells and smooth muscle cells. Proc Natl Acad Sci U S A. 1990 Jul;87(13):5134–5138. doi: 10.1073/pnas.87.13.5134. [DOI] [PMC free article] [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., Rucinski D., Oppenheim J. J., Kaplan A. P. Monocyte chemotactic and activating factor is a potent histamine-releasing factor for human basophils. J Exp Med. 1992 Feb 1;175(2):489–493. doi: 10.1084/jem.175.2.489. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nelken N. A., Coughlin S. R., Gordon D., Wilcox J. N. Monocyte chemoattractant protein-1 in human atheromatous plaques. J Clin Invest. 1991 Oct;88(4):1121–1127. doi: 10.1172/JCI115411. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Oppenheim J. J., Zachariae C. O., Mukaida N., Matsushima K. Properties of the novel proinflammatory supergene "intercrine" cytokine family. Annu Rev Immunol. 1991;9:617–648. doi: 10.1146/annurev.iy.09.040191.003153. [DOI] [PubMed] [Google Scholar]
- Rollins T. E., Springer M. S. Identification of the polymorphonuclear leukocyte C5a receptor. J Biol Chem. 1985 Jun 25;260(12):7157–7160. [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]
- Siciliano S. J., Rollins T. E., Springer M. S. Interaction between the C5a receptor and Gi in both the membrane-bound and detergent-solubilized states. J Biol Chem. 1990 Nov 15;265(32):19568–19574. [PubMed] [Google Scholar]
- Valente A. J., Rozek M. M., Schwartz C. J., Graves D. T. Characterization of monocyte chemotactic protein-1 binding to human monocytes. Biochem Biophys Res Commun. 1991 Apr 15;176(1):309–314. doi: 10.1016/0006-291x(91)90925-w. [DOI] [PubMed] [Google Scholar]
- Ylä-Herttuala S., Lipton B. A., Rosenfeld M. E., Särkioja T., Yoshimura T., Leonard E. J., Witztum J. L., Steinberg D. Expression of monocyte chemoattractant protein 1 in macrophage-rich areas of human and rabbit atherosclerotic lesions. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5252–5256. doi: 10.1073/pnas.88.12.5252. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yoshimura T., Leonard E. J. Identification of high affinity receptors for human monocyte chemoattractant protein-1 on human monocytes. J Immunol. 1990 Jul 1;145(1):292–297. [PubMed] [Google Scholar]
- Zachariae C. O., Anderson A. O., Thompson H. L., Appella E., Mantovani A., Oppenheim J. J., Matsushima K. Properties of monocyte chemotactic and activating factor (MCAF) purified from a human fibrosarcoma cell line. J Exp Med. 1990 Jun 1;171(6):2177–2182. doi: 10.1084/jem.171.6.2177. [DOI] [PMC free article] [PubMed] [Google Scholar]