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Structure
and Function of Chemokine Receptors 
Our laboratory studies chemokines and chemokine receptors. Chemokines
are small, heparin-binding proteins and are potent chemoattractants of
leukocytes. Chemokines are thought to be involved in a wide spectrum of
human disease, including atherosclerosis and AIDS. We were the first to
clone CCR2, the receptor for MCP-1. Much of the work in the laboratory
over the past several years has focused on the elucidation of ligand binding
domains and signal transduction pathways of this receptor.
We have also devoted attention to CCR5, a coreceptor for leuko-cyte infection
by HIV-l strains with a preference for macrophages. We have shown that
HIV-1 interacts with multiple extracellular domains of CCR5, and have
further shown that signal-ing by CCR5 is not critical for coreceptor activity.
We have recently created CCR2-deficient mice.These mice are phenotypically
normal when raised under aseptic conditions, but exhibit profound defects
in recruitment of monocytes/ macrophages to sites of inflammation or injury.
During the past year, we crossed the CCR2-deficient mice with apo-E knockouts,
a line of mice genetically altered to develop severe atherosclerosis.
Preliminary results suggest that the absence of CCR2 confers protection
against atherogenesis in these double-knockout animals.
Selected Publications:
Boring, L, Gosling, J, Chensue, S, Kunkel, SL, Farese, RV, Broxmeyer,
HE, and Charo, IF. Impaired monocyte migration and reduced Type 1 (Th1)
responses in CCR2 knockout mice. J. Clin. Invest. 100 (1997): 2552-2561.
Arai, H, Tsou, CL, and Charo IF. Chemotaxis in a lymphocyte cell line
transfected with C-C chemokine receptor 2 (CCR2B): Evidence that directed
migration is mediated by §g dimers released by activation of Gai-coupled
receptors. Proc. Natl. Sci. USA 94 (1997): 14495-14499.
Atchison, RE,
Gosling, J, Monteclaro, FS, Franci, C, Digilio, L, Charo, IF., Goldsmith,
MA. Multiple extracellular elements of CCRS and HIV-1 entry: Dissociation
from response to chemokines. Science 274 (1996): 1924-1926.
Contact Information:
Email: icharo@gladstone.ucsf.edu
Phone: (415) 695-3782
Address: Box 1230, MB, 1650 Owens Street
The University of California, San Francisco, CA 94143, (415) 476-9000
Copyright 2003, The Regents of the University of California.
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