1. Sodium Sulfite-Induced Mast Cell Pyroptosis and Degranulation
Jing Lu, Shuting Yang, Shuang Guan, Meitong Liu, Xiaolei Shi, Jing Yu, Yuelin Chen, YaZhuo Li J Agric Food Chem . 2021 Jul 14;69(27):7755-7764. doi: 10.1021/acs.jafc.1c02436.
Sodium sulfite, a common food additive, has been proved to cause allergic reaction. Pyroptosis is an inflammatory form of programmed cell death with plasma membrane lysis. In this study, we found that sodium sulfite triggered pyroptosis, which depended on reactive oxygen species (ROS)/NOD-like receptor protein 3 (NLRP3) in RBL-2H3 mast cells. Sodium sulfite increased the generation of ROS and the expression of NLRP3, caspase-1, gasdermin D N-terminal (GSDMD-N), interleukin-1β (IL-1β), and interleukin-18 (IL-18). The ROS scavenger N-acetyl-L-carnosine (NAC) and the NLRP3 inhibitor MCC950 reversed these effects. Furthermore, using a lactate dehydrogenase kit, propidium iodide staining, scanning electron microscopy, colocalization of GSDMD-N with histamine, and neutral red staining, we found that sodium sulfite notably induced cell membrane rupture. Because β-Hexosaminidase and histamine play a key role in allergic reactions, we detected the release of β-Hexosaminidase and histamine. The data showed that the release of β-Hexosaminidase and histamine induced by sodium sulfite was increased with dose independence, which were inhibited after treatment with NAC or MCC950. Overall, evidence suggested that pyroptosis induced by sodium sulfite may rupture the cell membrane and result in degranulation of mast cells. Our study may provide new insights for the mechanism by which sodium sulfite induces mast cell death and sensitization.
2. Histamine secretion induced by N-acetyl cysteine
K E Barrett, D D Metcalfe, J R Minor Agents Actions . 1985 Apr;16(3-4):144-6. doi: 10.1007/BF01983123.
The mucolytic drug N-acetyl cysteine has been shown to release histamine from cultured mouse mast cells and from human basophils. At neutral pH the release was moderate and non-cytotoxic. If the acidity of the drug was not neutralized, this histamine release was markedly potentiated, but was then associated with a reduction in the viability of the cells. However, the high level of release could not be reproduced by simply exposing the cells to an acidic medium. The results are discussed in terms of a possible mechanism for the adverse reactions sometimes observed during N-acetyl cysteine therapy.
3. Putative mechanism for guinea pig ileum contraction by N-formyl peptides. A comparative study of N-formyl and N-acetyl peptides with the N-terminal sequence of the calpain small subunit
M Sasaki, M Kunimatsu, X J Ma, Y Ozaki, S Fujimoto Life Sci . 1995;57(5):463-71. doi: 10.1016/0024-3205(95)00280-j.
N-formyl and N-acetyl peptides with the N-terminal sequence of the calpain small subunit were prepared and their spasmogenic activity was examined using guinea pig ileum preparations. Sections of ileum were found to contract in the presence of all N-formyl peptides used (tri- to nonapeptides and tridecapeptide) but failed to contract with N-acetyl peptides, although both N-formyl and N-acetyl peptides have chemotactic activity, indicating that spasmogenic activity and chemotactic activity involve different mechanisms. A formyl peptide antagonist, Boc-Phe-Leu-Phe-Leu-Phe, suppressed contraction by formyl peptides whereas a histamine antagonist, diphenhydramine, suppressed contraction by formyl peptides as well as by histamine. In addition, formyl peptide-induced contractions were noted after an approximately 20-sec time lag, and their profiles were bell-shaped and roughly symmetrical. On the other hand, histamine- and acetylcholine-induced contractions exhibited a much shorter time lag. These data led us to conclude that contraction induced by formyl peptides may not occur as a direct response but may be due to the histamine released from mast cells present in the tissues of the small intestine.
