CCR1 expression and signal transduction by murine BMMC results in secretion of TNF-α, TGFβ-1 and IL-6 (98.10)

Abstract

Abstract Chemokine receptors are important co-stimulatory molecules found on many blood cells. Chemokine receptor 1 (CCR1) is one of the important chemokine receptor identified in different immune cells known for its function in various diseases. The expression and functions of chemokine receptors 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 mRNA and protein for CCR1. BMMC cultured in the presence of murine recombinant stem cell factor and murine interleukin-3 expressed CCR1 after 5-6 weeks. Co-stimulation of CCR1 by its ligand macrophage inflammatory protein 1α (MIP-1α) and the IgE receptor FceRI enhanced BMMC degranulation compared to FceRI stimulation alone (85% vs. 54%, p < 0.0001) and Ca2+ influx. We report for the first time that mBMMCCCR1+ cells endogenously express neurokinin receptor-1 and intercellular adhesion molecule-1. We also observed significant increases in mast cell secretion of key growth factors, cytokines and chemokine mediators upon CCR1- FceRI co-stimulation. These factors include transforming growth factor β-1, tumor necrosis factor-α, ciliary neurotrophic factor and the cytokine interleukin-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.