• 主页
  • 查找结果
  • Oxidation by neutrophils-derived HOCl increases immunogenicity of proteins by converting them into ligands of several endocytic receptors involved in antigen uptake by dendritic cells and macrophages.

Oxidation by neutrophils-derived HOCl increases immunogenicity of proteins by converting them into ligands of several endocytic receptors involved in antigen uptake by dendritic cells and macrophages.

PloS one (2015-04-08)
Rafał Biedroń, Maciej K Konopiński, Janusz Marcinkiewicz, Szczepan Józefowski
摘要

The initiation of adaptive immune responses to protein antigens has to be preceded by their uptake by antigen presenting cells and intracellular proteolytic processing. Paradoxically, endocytic receptors involved in antigen uptake do not bind the majority of proteins, which may be the main reason why purified proteins stimulate at most weak immune responses. A shared feature of different types of adjuvants, capable of boosting immunogenicity of protein vaccines, is their ability to induce acute inflammation, characterized by early influx of activated neutrophils. Neutrophils are also rapidly recruited to sites of tissue injury or infection. These cells are the source of potent oxidants, including hypochlorous acid (HOCl), causing oxidation of proteins present in inflammatory foci. We demonstrate that oxidation of proteins by endogenous, neutrophils-derived HOCl increases their immunogenicity. Upon oxidation, different, randomly chosen simple proteins (yeast alcohol dehydrogenase, human and bovine serum albumin) and glycoproteins (human apo-transferrin, ovalbumin) gain the ability to bind with high affinity to several endocytic receptors on antigen presenting cells, which seems to be the major mechanism of their increased immunogenicity. The mannose receptor (CD206), scavenger receptors A (CD204) and CD36 were responsible for the uptake and presentation of HOCl-modified proteins by murine dendritic cells and macrophages. Other scavenger receptors, SREC-I and LOX-1, as well as RAGE were also able to bind HOCl-modified proteins, but they did not contribute significantly to these ligands uptake by dendritic cells because they were either not expressed or exhibited preference for more heavily oxidised proteins. Our results indicate that oxidation by neutrophils-derived HOCl may be a physiological mechanism of conferring immunogenicity on proteins which in their native forms do not bind to endocytic receptors. This mechanism might enable the immune system to detect infections caused by pathogens not recognized by pattern recognition receptors.

材料
货号
品牌
产品描述

Sigma-Aldrich
过氧化氢 溶液, 30 % (w/w) in H2O, contains stabilizer
Sigma-Aldrich
羟乙基哌嗪乙硫磺酸, ≥99.5% (titration)
Sigma-Aldrich
过氧化氢 溶液, contains inhibitor, 30 wt. % in H2O, ACS reagent
Sigma-Aldrich
羟乙基哌嗪乙硫磺酸, BioPerformance Certified, ≥99.5% (titration), suitable for cell culture
Sigma-Aldrich
次氯酸钠 溶液, reagent grade, available chlorine 10-15 %
Sigma-Aldrich
次氯酸钠 溶液, reagent grade, available chlorine 4.00-4.99 %
Sigma-Aldrich
过氧化氢 溶液, 50 wt. % in H2O, stabilized
Millipore
过氧化氢 溶液, 3%, suitable for microbiology
Sigma-Aldrich
L-谷氨酰胺, meets USP testing specifications, suitable for cell culture, 99.0-101.0%, from non-animal source
Supelco
过氧化氢 溶液, ≥30%, for trace analysis
Sigma-Aldrich
HEPES缓冲溶液, 1 M in H2O
Sigma-Aldrich
L-谷氨酰胺, ReagentPlus®, ≥99% (HPLC)
SAFC
羟乙基哌嗪乙硫磺酸
SAFC
L-谷氨酰胺
Sigma-Aldrich
过氧化氢 溶液, contains ~200 ppm acetanilide as stabilizer, 3 wt. % in H2O
Supelco
过氧化氢 溶液, 30 % (w/w), for ultratrace analysis
Sigma-Aldrich
D-(+)-甘露糖, powder, BioReagent, suitable for cell culture
Sigma-Aldrich
邻苯二胺 二盐酸盐, tablet, 10 mg substrate per tablet
Sigma-Aldrich
利多卡因, powder
Sigma-Aldrich
羟乙基哌嗪乙硫磺酸, BioUltra, for molecular biology, ≥99.5% (T)
Sigma-Aldrich
过氧化氢 溶液, 34.5-36.5%
Supelco
利多卡因, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
D-(+)-甘露糖, synthetic, ≥99%
Sigma-Aldrich
过氧化氢溶液, 30% (w/w), puriss. p.a., reag. ISO, reag. Ph. Eur.
Sigma-Aldrich
过氧化氢 溶液, contains inhibitor, 30 wt. % in H2O, meets USP testing specifications
SAFC
羟乙基哌嗪乙硫磺酸
Sigma-Aldrich
羟乙基哌嗪乙硫磺酸, BioXtra, pH 5.0-6.5 (1 M in H2O), ≥99.5% (titration)
Sigma-Aldrich
肿瘤坏死因子-α 来源于小鼠, TNF-α, recombinant, expressed in E. coli, powder, suitable for cell culture
Sigma-Aldrich
L-谷氨酰胺, BioUltra, ≥99.5% (NT)
Sigma-Aldrich
过氧化氢 溶液, contains inhibitor, 35 wt. % in H2O