ABSTRACT
Continuous and excessive use of organophosphorus compounds (OPs) has led to environmental contaminations which raise public concerns. This study investigates the isotope fractionation patterns of OPs in the aquatic environment dependence upon hydrolysis, photolysis and radical oxidation processes. The hydrolysis of parathion (EP) and methyl parathion (MP) resulted in significant carbon fractionation at lower pH (pH2-7, εC=-6.9~-6.0 for EP, -10.5~-9.9 for MP) but no detectable carbon fractionation at higher pH (pH12). Hydrogen fractionation was not observed during any of the hydrolysis experiments. These results indicate that compound specific isotope analysis (CSIA) allows distinction of two different pH-dependent pathways of hydrolysis. Carbon and hydrogen isotope fractionation were determined during UV/H2O2 photolysis of EP and tris(2-chloroethyl) phosphate (TCEP). The constant δ2H values determined during the OH radical reaction of EP suggested that the rate-limiting step proceeded through oxidative attack by OH radical on the PS bond. The significant H isotope enrichment suggested that OH radical oxidation of TCEP was caused by an H-abstraction during the UV/H2O2 processes (εH=-56±3). Fenton reaction was conducted to validate the H isotope enrichment of TCEP associated with radical oxidation, which yielded εH of -34±5. Transformation products of OPs during photodegradation were identified using Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS). This study highlights that the carbon and hydrogen fractionation patterns have the potential to elucidate the transformation of OPs in the environment.
ABSTRACT
Adenylate cyclase toxin (CyaA) is a key virulence factor of the whooping cough agent Bordetella pertussis. The toxin targets CD11b-expressing phagocytes and delivers into their cytosol an adenylyl cyclase (AC) enzyme that subverts cellular signaling by increasing cAMP levels. In the present study, we analyzed the modulatory effects of CyaA on adhesive, migratory and antigen presenting properties of Toll-like receptor (TLR)-activated murine and human dendritic cells (DCs). cAMP signaling of CyaA enhanced TLR-induced dissolution of cell adhesive contacts and migration of DCs towards the lymph node-homing chemokines CCL19 and CCL21 in vitro. Moreover, we examined in detail the capacity of toxin-treated DCs to induce CD4(+) and CD8(+) T cell responses. Exposure to CyaA decreased the capacity of LPS-stimulated DCs to present soluble protein antigen to CD4+ T cells independently of modulation of co-stimulatory molecules and cytokine production, and enhanced their capacity to promote CD4(+)CD25(+)Foxp3(+) T regulatory cells in vitro. In addition, CyaA decreased the capacity of LPS-stimulated DCs to induce CD8(+) T cell proliferation and limited the induction of IFN-γ producing CD8(+) T cells while enhancing IL-10 and IL-17-production. These results indicate that through activation of cAMP signaling, the CyaA may be mobilizing DCs impaired in T cell stimulatory capacity and arrival of such DCs into draining lymph nodes may than contribute to delay and subversion of host immune responses during B. pertussis infection.
