Human Mast Cells Transmigrate Through Human Umbilical Vein Endothelial Monolayers and Selectively Produce IL-8 in Response to Stromal Cell-Derived Factor-1α

Abstract

Mature mast cells are generally considered to be less mobile cells residing within tissue sites. However, mast cell numbers are known to increase in the context of inflammation, and mast cells are recognized to be important in regulating local neutrophil infiltration. CXC chemokines may play a critical 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 regulating mast cell migration and mediator production. It was demonstrated that human mast cells constitutively express mRNA and protein for CXCR4. Stimulation of human mast cells with SDF-1, the only known ligand for CXCR4, induced a significant increase in intracellular calcium levels. In vitro, SDF-1α mediated dose-dependent migration of human cord blood-derived mast cells and HMC-1 cells across HUVEC monolayers. Although SDF-1α did not induce mast cell degranulation, it selectively stimulated production of the neutrophil chemoattractant IL-8 without affecting TNF-α, IL-1β, IL-6, GM-CSF, IFN-γ, or RANTES production, providing further evidence of the selective modulation of mast cell function by this chemokine. These findings provide a novel, SDF-1-dependent mechanism for mast cell transendothelial migration and functional regulation, which may have important implications for the local regulation of mast cells in disease.

Stimuli from Conspecifics Influence Brain Mast Cell Population in Male Rats

“…In the brain, SDF-1 was shown to induce the migration of microglial cells and astrocytes (Tanabe, Heesen, Yoshizawa, Berman, Luo, Bleul, Springer, Okuda, Gerard, and Dorf, 1997). However, this ligand has also been shown to be a potent chemoattractant for mast cells and to facilitate mast cell transmigration through the umbilical cord blood vessel lamina without inducing degranulation (Lin, Issekutz, and Marshall, 2000). Only two arteries, the dorsal thalamic artery and the anterior choroidal artery, supply the dorsal thalamus (Scremin, 1995), in particular the nuclei in which mast cells increased in number during the pairing situations in our study.…”

Pseudomonas aeruginosaActivates Human Mast Cells to Induce Neutrophil Transendothelial Migration Via Mast Cell-Derived IL-1α and β

“…Highly purified CBMC were obtained by long-term culture of cord blood progenitor cells, as previously described (16,17). After Ͼ8 wk in culture, mature MC (Ͼ95% purity) were identified by their morphological features and the presence of metachromatic granules (toluidine blue staining).…”

“…HUVEC were isolated and cultured in gelatin-coated flasks and grown on filters, as previously described (16,20,21). The HUVEC formed a tight permeability barrier in 5-6 days and were evaluated for barrier function by 125 I-labeled human serum albumin (HSA) diffusion, as previously described (20,21).…”

Bone marrow stromal cells and the upregulation of interleukin-8 production in human T-cell acute lymphoblastic leukemia through the CXCL12/CXCR4 axis and the NF- B and JNK/AP-1 pathways

“…DNA binding activity of nuclear proteins from primary T-ALL cells was determined using [γ- 32 P]ATP endlabeled double-strand oligonucleotide encompassing the NF-κB binding site of the IL-8 promoter as the probe (5'-GTGGAATTTCC-3'). A radiolabeled probe (0.04 pmol; specific activity ~3x10 6 cpm/pmol) was added to nuclear extracts (5 µg) in binding buffer.…”

“…[28][29][30] CXCL12 also induces the expression of vascular endothelial growth factor in T-ALL cell lines 31 and regulates IL-8 production in human mast cells, endothelial cells and fibroblast-like synoviocytes. [32][33][34] Nonetheless, there is very little information on the molecular mechanisms leading to the regulation of gene expression by CXCL12.…”