Glufosinate aerogenic exposure induces glutamate and IL-1 receptor dependent lung inflammation.

Glufosinate-ammonium (GLA), the active component of an herbicide, is known to cause neurotoxicity. GLA shares structural analogy with glutamate. It is a powerful inhibitor of glutamine synthetase (GS) and may bind to glutamate receptors. Since these potentials targets of GLA are present in lung and immune cells, we asked whether airway exposure to GLA may cause lung inflammation in mice. A single GLA exposure (1 mg/kg) induced seizures and inflammatory cell recruitment in the broncho-alveolar space, and increased myeloperoxidase (MPO), inducible NO synthase (iNOS), interstitial inflammation and disruption of alveolar septae within 6-24 h. Interleukin 1ß (IL-1ß) was increased and lung inflammation depended on IL-1 receptor 1 (IL-1R1). We demonstrate that glutamate receptor pathway is central, since the N-methyl-D-aspartate (NMDA) receptor inhibitor MK-801 prevented GLA-induced lung inflammation. Chronic exposure (0.2 mg/kg 3× per week for 4 weeks) caused moderate lung inflammation and enhanced airway hyperreactivity with significant increased airway resistance. In conclusion, GLA aerosol exposure causes glutamate signalling and IL-1R-dependent pulmonary inflammation with airway hyperreactivity in mice.

[Synthesis and identification of sulfonamides artificial antigen].

OBJECTIVE: To synthesise N-sulfanil-4-aminobutyric acid mother nucleus derivative of sulfonamides, and its artificial antigens in order to explore the methods of preparation were discussed. METHODS: N-sulfanil-4-aminobutyric acid was synthesized and confirmed by 1HNMR, 13CNMR, IR, ESI-MS. N-sulfanil-4-aminobutyric acid artificial antigen was synthesized by the methods of active ester coupling, and was identified by UV scan. Single factor test and orthogonal test design methods L9(3(3)) were employed to study the influence of the factors such as the initial molar ratio of reagents, activate hapten time and the coupling time to the coupling rate, as to determine the optimal reaction conditions for synthesis. The obtained results showed that the initial molar ratio of hapten to BSA 50:1, activated hapten time 6 hours, coupling time 4 hours. The artificial antigen was prepared by the optimal reaction conditions. The artificial antigen was injected into Balb/c mice and the blood samples were obtained from tails of Balb/c mice after the 5th injection and detected by iELISA method. RESULTS: The structure of N-sulfanil-4-aminobutyric acid was correct. The artificial antigen was prepared. CONCLUSION: Antigens was acquired successfully.

Infection control by antibody disruption of bacterial quorum sensing signaling.

Quorum sensing (QS) is the process through which bacteria communicate utilizing small diffusible molecules termed autoinducers. It has been demonstrated that QS controls a plethora of microbial processes including the expression of virulence factors. Here we report an immunopharmacotherapeutic approach for the attenuation of QS in the Gram-positive human pathogen Staphylococcus aureus. An anti-autoinducer monoclonal antibody, AP4-24H11, was elicited against a rationally designed hapten, and efficiently inhibited QS in vitro through the sequestration of the autoinducing peptide (AIP)-4 produced by S. aureus RN4850. Importantly, AP4-24H11 suppressed S. aureus pathogenicity in an abscess formation mouse model in vivo and provided complete protection against a lethal S. aureus challenge. These findings provide a strong foundation for further investigations of immunopharmacotherapy for the treatment of bacterial infections in which QS controls the expression of virulence factors.