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Related Collections Neoplasia Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 June 2001, Vol. 97, No. 11, pp. 3349-3353 CHEMOKINES Macrophage inflammatory protein-1 is an osteoclastogenic factor in myeloma that is independent of receptor activator of nuclear factor B ligand Je-Ho Han, Sun Jin Choi, Noriyoshi Kurihara, Masanori Koide, Yasuo Oba, and G. David Roodman From the Department of Medicine/Hematology, University of Texas Health Science Center, San Antonio, and the General Clinical Research Center and Research Service of the Audie L. Murphy Veterans Administration Hospital, San Antonio, Texas. A complementary DNA expression library derived from marrow samples from myeloma patients was recently screened and human macrophage inflammatory protein-1 (hMIP-1) was identified as an osteoclastogenic factor expressed in these samples. hMIP-1 enhanced osteoclast (OCL) formation in human marrow cultures and by highly purified OCL precursors in a dose-dependent manner (5-200 pg/mL). Furthermore, hMIP-1 enhanced OCL formation induced by human interleukin-6 (IL-6), which is produced by marrow stromal cells when they interact with myeloma cells. hMIP-1 also enhanced OCL formation induced by parathyroid hormone-related protein (PTHrP) and receptor activator of nuclear factor B ligand (RANKL), factors also implicated in myeloma bone disease. Time-course studies revealed that the hMIP-1 acted during the last 2 weeks of the 3-week culture period. Reverse transcription-polymerase chain reaction analysis showed that the chemokine receptors for hMIP-1 (CCR1 and CCR5) were expressed by human bone marrow and highly purified early OCL precursors. Furthermore, hMIP-1 did not increase expression of RANKL. These data demonstrate that hMIP-1 is an osteoclastogenic factor that appears to act directly on human OCL progenitors and acts at the later stages of OCL differentiation. These data further suggest that in patients with myeloma, MIP-1 produced by myeloma cells, in combination with RANKL and IL-6 that are produced by marrow stromal cells in response to myeloma cells, enhances OCL formation through their combined effects on OCL precursors. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Kanayama, D. Kurotaki, J. Morimoto, T. Asano, Y. Matsui, Y. Nakayama, Y. Saito, K. Ito, C. Kimura, N. 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	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020