Mercury induces inflammatory mediator release from human mast cells

Background: mercury is known to be neurotoxic,but its effects on the immune system are less well known. mast cells are involved in allergic reactions,but also in innate and acquired immunity,as well as in inflammation. many patients with autism spectrum disorders (asd) have allergic symptoms; moreover,the prevalence of asd in patients with mastocytosis,characterized by numerous hyperactive mast cells in most tissues,is 10-fold higher than the general population suggesting mast cell involvement. we,therefore,investigated the effect of mercuric chloride (hgcl2) on human mast cell activation.methods: human leukemic cultured lad2 mast cells and normal human umbilical cord blood-derived cultured mast cells (hcbmcs) were stimulated by hgcl2 (0.1-10 μm) for either 10 min for beta-hexosaminidase release or 24 hr for measuring vascular endothelial growth factor (vegf) and il-6 release by elisa.results: hgcl2induced a 2-fold increase in β-hexosaminidase release,and also significant vegf release at 0.1 and 1 μm (311 ± 32 pg/106cells and 443 ± 143 pg/106cells,respectively) from lad2 mast cells compared to control cells (227 ± 17 pg/106cells,n = 5,p < 0.05). addition of hgcl2(0.1 μm) to the proinflammatory neuropeptide substance p (sp,0.1 μm) had synergestic action in inducing vegf from lad2 mast cells. hgcl2also stimulated significant vegf release (360 ± 100 pg/106cells at 1 μm,n = 5,p < 0.05) from hcbmcs compared to control cells (182 ± 57 pg/106cells),and il-6 release (466 ± 57 pg/106cells at 0.1 μm) compared to untreated cells (13 ± 25 pg/106cells,n = 5,p < 0.05). addition of hgcl2(0.1 μm) to sp (5 μm) further increased il-6 release.conclusions: hgcl2stimulates vegf and il-6 release from human mast cells. this phenomenon could disrupt the blood-brain-barrier and permit brain inflammation. as a result,the findings of the present study provide a biological mechanism for how low levels of mercury may contribute to asd pathogenesis. © 2010 kempuraj et al; licensee biomed central ltd.