Interaction between activated chemokine receptor 1 and FceRI at membrane rafts promotes communication and F-actin-rich cytoneme extensions between mast cells

• Published in: International immunology Vol. 22; no. 2; pp. 113 - 128
• Main Authors: Fifadara, Nimita H, Beer, Freddy, Ono, Shoichiro, Ono, Santa J
• Format: Journal Article
• Language: English
• Published: 01.02.2010
• DOI: 10.1093/intimm/dxp118
• ISSN: 0953-8178

Chemokines play important regulatory roles in immunity, but their contributions to mast cell function remain poorly understood. We examined the effects of FceRI-chemokine receptor (CCR) 1 co-stimulation on receptor localization and cellular morphology of bone marrow-derived mast cells. Whereas FceRI and CCR1 co-localized at the plasma membrane in unsensitized cells, sensitization with IgE promoted internalization of CCR1 molecules. Co-stimulation of FceRI and CCR1 with antigen and macrophage inflammatory protein-1a was more effective than FceRI stimulation alone in causing leading edge formation, flattened morphology, membrane ruffles and ganglioside (GM1 super(+)) lipid mediator release. Co-stimulation resulted in phalloidin-positive cytoneme-like cellular extensions, also known as tunneling nanotubes, which originated at points of calcium accumulation. This is the first report of cytoneme formation by mast cells. To determine the importance of lipid rafts for mast cell function, the cells were cholesterol depleted. Cholesterol depletion enhanced degranulation in resting, sensitized and co-stimulated cells, but not in FceRI-cross-linked cells, and inhibited formation of filamentous actin super(+) cytonemes but not GM1 super(+) cytonemes. Treatment with latrunculin A to sequester globular-actin abolished cytoneme formation. The cytonemes may participate in intercellular communication during allergic and inflammatory responses, and their presence in the co-stimulated mast cells suggests new roles for CCRs in immunopathology.