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International Immunology Advance Access originally published online on July 10, 2009
International Immunology 2009 21(8):991-1001; doi:10.1093/intimm/dxp066
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© The Japanese Society for Immunology. 2009. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

CCR1 expression and signal transduction by murine BMMC results in secretion of TNF-{alpha}, TGFβ-1 and IL-6

Nimita H. Fifadara1, Cho Cho Aye1, Sandeep K. Raghuwanshi2, Ricardo M. Richardson2 and Santa Jeremy Ono1

1 Department of Opthalmology, Dobbs Ocular Immunology Laboratories, Emory Eye Center, Emory University School of Medicine, Atlanta, GA 30322, USA
2 JLC-Biomedical/Biotechnology Research Institute, North Carolina Central University, Durham, NC 27707, USA

Correspondence to: N. Fifadara; E-mail: nfifada{at}emory.edu

Chemokine receptors (CCRs) are important co-stimulatory molecules found on many blood cells and associated with various diseases. The expression and function of CCRs on mast cells has been quite controversial. In this study, we report for the first time that murine bone marrow-derived mast cells (BMMC) express messenger RNA and protein for CCR1. BMMC cultured in the presence of murine recombinant stem cell factor and murine IL-3 expressed CCR1 after 5–6 weeks. We also report for the first time that mBMMCCCR1+ cells endogenously express neurokinin receptor-1 and intercellular adhesion molecule-1. To examine the activity of CCR1 on these BMMC, we simultaneously stimulated two receptors: CCR1 by its ligand macrophage inflammatory protein-1{alpha} and the IgE receptor Fc{varepsilon}RI by antigen cross-linking. We found that co-stimulation enhanced BMMC degranulation compared with Fc{varepsilon}RI stimulation alone, as assessed by β-hexosaminidase activity (85 versus 54%, P < 0.0001) and Ca2+ influx (223 versus 183 nM, P < 0.05). We also observed significant increases in mast cell secretion of key growth factors, cytokines and chemokine mediators upon CCR1–Fc{varepsilon}RI co-stimulation. These factors include transforming growth factor β-1, tumor necrosis factor-{alpha} and the cytokine IL-6. Taken together, our data indicate that CCR1 plays a key role in BMMC function. These findings contribute to our understanding of mechanisms for immune cell trafficking during inflammation.

Keywords: chemokines, co-stimulation, cytokines, Fc receptors, mast cells


Transmitting editor: I. Pecht

Received 9 October 2008, accepted 10 June 2009.


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