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Chemokine Biology — Basic Research and Clinical Application pp 103–113Cite as

Current status of CCR1 antagonists in clinical trials

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Part of the book series: Progress in Inflammation Research ((PIR))

Abstract

The chemokine receptor, CCR1, is believed to play a crucial role in the migration of leukocytes to sites of inflammation. It has been shown to be expressed on monocytes, T cells, dendritic cells, and in some cases, neutrophils [1–4]) and interacts with at least 7 different ligands including CCL3 (MIP-1α, macrophage inflammatory protein-1α), CCL5 (RANTES, regulated on activation, normal T cell expressed and secreted), CCL7 (MCP-3, monocyte chemotactic protein-3), CCL14 (HCC-1, hemofiltrate C-C chemokine-1), CCL8 (MCP-2, monocyte chemotactic protein-2), CCL15 (leukotactin-1), and CCL23 (MPIF, myeloid progenitor inhibitory factor-1) [5, 6]. These ligands have been shown to have potent chemotactic activity in vitro [4] and, in some cases in vivo where intradermal injection of CCL3 or CCL5 induced a robust cellular infiltration [3, 7]. Further, these chemokines can be produced by the very cells they attract to inflammatory sites. For example, peripheral blood monocytes can secrete CCL3 following activation, potentially setting up an amplification loop whereby monocytes migrate into tissue in response to CCR1, then become activated and secrete CCR1 ligands such as CCL3, thereby recruiting more cells and setting up a state of chronic inflammation. These properties suggest that CCR1 may play an important role in perpetuating inflammatory responses.

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Authors and Affiliations

  1. Department of Antibacterials, Immunology, and Cancer, MS 8220-2410, Pfizer Global Research and Development, Eastern Point Road, Groton, CT, 06340, USA

    Ronald P. Gladue & Matthew F. Brown

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  1. Ronald P. Gladue
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  2. Matthew F. Brown
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Editors and Affiliations

  1. Lilly Corporate Center, Cancer Inflammation and Cell Survival Eli Lilly and Company, Indianapolis, IN, 46285, USA

    Kuldeep Neote

  2. NitroMed, Inc., 12 Oak Park Drive, Bedford, MA, 01730, USA

    Gordon L. Letts

  3. Theodor Koch Institute, University of Bern, Freiestrasse 1, 3012, Bern, Switzerland

    Bernhard Moser

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© 2007 Birkhäuser Verlag Basel/Switzerland

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Gladue, R.P., Brown, M.F. (2007). Current status of CCR1 antagonists in clinical trials. In: Neote, K., Letts, G.L., Moser, B. (eds) Chemokine Biology — Basic Research and Clinical Application. Progress in Inflammation Research. Birkhäuser Basel. https://doi.org/10.1007/978-3-7643-7437-2_8

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