Correlation between mast cell-mediated allergic inflammation and length of perfluorinated compounds

Perfluorinated compounds (PFC) have widely been used in numerous applications including clothing, food packaging, and nonstick coating. With the widespread use of PFC, concerns regarding potential adverse health effects in humans and wildlife have increased. In spite of the known PFC-mediated immunotoxiciy, correlation with PFC and allergic inflammation still requires elucidation. The aim of this study was to examine the effect of four types of PFC (perfluoroheptanoic acid [PFHpA], perfluorononanoic acid [PFNA], perfluorodecanoic acid [PFDA], and perfluoroundecanoic acid [PFUnA]) on mast cell-mediated allergic inflammation in the presence of high-affinity immunoglobulin (Ig) E receptor (FcεRI) cross-linking. Among PFC family, long-chain PFDA and PFUnA increased release of histamine and β-hexosaminidase by up-regulation of intracellular calcium levels in IgE-stimulated mast cells. In addition, PFDA and PFUnA enhanced gene expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 by activation of nuclear factor-κB in IgE-stimulated mast cells. In ovalbumin (OVA)-induced model of systemic anaphylaxis in the presence of hypothermia, PFNA, PFDA, and PFUnA exacerbated allergic symptoms accompanied by elevation in serum histamine, TNF-α, IgE, and IgG₁. Our data indicate that some PFC aggravated high-affinity IgE receptor (FcεRI)-mediated mast cell degranulation and allergic symptoms. Consequently, the results demonstrated that carbon-chain length of PFC may serve as a factor in allergic inflammation.