Human mast cells transmigrate through human umbilical vein endothelial monolayers and selectively produce IL-8 in response to stromal cell-derived factor-1 alpha

Mature mast cells are generally considered to be less mobile cells residing within tissue sites. However, mast cell numbers are known to increase in t he context of inflammation, and mast cells are recognized to be important i n regulating local neutrophil infiltration. CXC chemokines may play a criti cal role in this process. In this study two human mast cell-like Lines, HMC -1 and KU812, and human cord blood-derived primary cultured mast cells were employed to examine role of stromal cell-derived factor-1 (SDF-1) in regul ating mast cell migration and mediator production. It was demonstrated that human mast cells constitutively express mRNA and protein for CXCR4, Stimul ation of human mast cells with SDF-1, the only known ligand for CXCR4, indu ced a significant increase in intracellular calcium levels. In vitro, SDF-1 alpha mediated dose-dependent migration of human cord blood-derived mast c ells and HMC-1 cells across HUVEC monolayers. Although SDF-1 alpha did not induce mast cell degranulation, it selectively stimulated production of the neutrophil chemoattractant IL-8 without affecting TNF-alpha, IL-1 beta, IL -6, GM-CSF, IFN-gamma, or RANTES production, providing further evidence of the selective modulation of mast cell function by this chemokine, These fin dings provide a novel, SDF-1-dependent mechanism for mast cell transendothe lial migration and functional regulation, which may have important implicat ions for the local regulation of mast cells in disease.