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Receptors and transduction pathways for monocyte chemotactic protein-2 and monocyte chemotactic protein-3. Similarities and differences with MCP-1.
Abstract
MCP-2 and MCP-3 are recently identified members of the Cys-Cys chemokine family with high sequence similarity with MCP-1 (62% and 71%, respectively). The present study was aimed at defining receptor usage and signal transduction pathways of MCP-2 and MCP-3 in human monocytes in comparison with MCP-1. MCP-2 and MCP-3 induced migration of monocytes with a typical bell-shaped curve and maximal response at 10 and 50 ng/ml, respectively. The maximal response elicited by MCP-2 and MCP-3 was lower (approximately 60%) than that of MCP-1. Pertussis toxin (PTox) inhibited the chemotactic activity of MCP-3 and MCP-1 (IC50 = 6.2 and 4.4 ng/ml, respectively), whereas cholera toxin (CTox) had little effect on these two chemokines (IC50 > 1000 ng/ml). In contrast, MCP-2-induced chemotaxis was blocked by CTox (IC50 = 75 ng/ml) and relatively unaffected by PTox. MCP-3 and MCP-1 induced a rapid increase in intracellular Ca2+ concentration, whereas MCP-2, in the range of concentrations active on chemotaxis, did not. MCP-1-, MCP-2-, and MCP-3-induced chemotactic responses were blocked by C-I, a serine/threonine kinase inhibitor, and by genistein, a tyrosine kinase inhibitor, with the MCP-2 response being more sensitive than those induced by MCP-1 and MCP-3. MCP-1 and MCP-3 rapidly induced arachidonic acid release whereas MCP-2 was ineffective. MCP-1 and MCP-3 cross-desensitized with each other in terms of Ca2+ transients and displaced with a comparable efficiency labeled MCP-1 from human monocytes. On the other hand, MCP-2 did not cross-desensitize with MCP-1 and MCP-3 and only partially (20%) displaced labeled MCP-1. Thus, in spite of high sequence similarity, MCP-2 differed considerably from MCP-1 and MCP-3 in terms of sensitivity to CTox and PTox, arachidonate and calcium mobilization, and capacity to compete for labeled MCP-1.
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Cited by
Monocyte chemotactic protein-1 (MCP-1), -2, and -3 are chemotactic for human T lymphocytes.
Taub, D. D., Proost, P., Murphy, W. J., Anver, M., Longo, D. L., van Damme, J., & Oppenheim, J. J. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117788 · Cited by 346
Self-citationImai, T., Yoshida, T., Baba, M., Nishimura, M., Kakizaki, M., & Yoshie, O. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.35.21514 · Cited by 310
(1999) · PubMed · Cited by 207
de Pablos, R. M., Herrera, A. J., Espinosa-Oliva, A. M., Sarmiento, M., Muñoz, M. F., Machado, A., & Venero, J. L. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-34 · Cited by 201
Martinez de la Torre, Y., Buracchi, C., Borroni, E. M., Dupor, J., Bonecchi, R., Nebuloni, M., Pasqualini, F., Doni, A., Lauri, E., Agostinis, C., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0607514104 · Cited by 178
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Metadata
- Authors
- Sozzani, S., Zhou, D., Locati, M., Rieppi, M., Proost, P., Magazin, M., Vita, N., van Damme, J., & Mantovani, A.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1994-04-01
- Volume
- 152
- Issue
- 7
- Pages
- 3615-3622
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1524916563
- Cited by
- 189
- References
- 0
- FWCI
- 5.77
- Type
- journal article
- Language
- en
- Open access
- closed
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- Sozzani, S., Zhou, D., Locati, M., Rieppi, M., Proost, P., Magazin, M., Vita, N., van Damme, J., & Mantovani, A. (1994). Receptors and transduction pathways for monocyte chemotactic protein-2 and monocyte chemotactic protein-3. Similarities and differences with MCP-1. The Journal of Immunology. https://doi.org/10.4049/jimmunol.152.7.3615
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