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CC chemokine receptor 1 (CCR1) is expressed by bone marrow mast cells (BMMC) and, when costimulated with FcεRI, increases cell activation and promotes reorganization of membrane rafts
Author(s) -
Goyal Nimita F,
Beer Frederick,
Morohoshi Kei,
Raghuwanshi Sandeep,
Aye Cho Cho,
Ohbayashi Masaharu,
Fukuda Ken,
Richardson Ricardo
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1075.14
Subject(s) - microbiology and biotechnology , degranulation , homing (biology) , ccr1 , chemokine receptor , cc chemokine receptors , chemistry , chemokine , lipid raft , receptor , biology , immunology , signal transduction , immune system , biochemistry , ecology
We examined functions and spatial interactions of FCεRI and CCR1 during granulocyte activation, in BMMC. Using flow cytometry and mRNA analysis, we observed that BMMC endogenously express CCR1 after 6 weeks. BMMC also expressed FCεRI and c‐kit, but not CCR2, CCR3 or CCR4. Using β‐hex, we found that costimulation of FCεRI and CCR1 using antigen and MIP‐1α resulted in significantly higher BMMC degranulation compared to crosslinking‐mediated FC ε RI activation alone (90% vs. 54%, P<0.05). We observed that Ca2+ influx increased from 183 nM with FCεR activation to 223 nM with costimulation in 7‐week BMMC (P<0.05). When we examined the spatial arrangement of these receptors, we found that sensitization alone, promoted CCR1 internalization. Subsequent cross‐linking to activate FCεRI resulted in lipid mediator release and localization of all FCεRI to reorganized, GM1‐positive membrane raft clusters. FCεRI‐CCR1 costimulation resulted extensive leading edge, flattening morphology and membrane ruffles than did FCεRI stimulation alone, lipid mediator released with higher frequency and cell‐to‐cell connections in a pattern seen exclusively with costimulation. The cell networks produced by costimulation may explain the arrest of mast cell chemotaxis in late‐phase allergic reactions, and may provide a conduit for cell‐cell crosstalk molecules and signal transduction mediators during immune reactions.