| Abstract: | RATIONALE: In a seemingly complex network of cellular and molecular regulations under stress or exposure to environmental allergens and pollutants are known to play a pivotal role in initiating and amplifying airway inflammation. To investigate the association between airway inflammation and phospholipid remodeling, Lysophosphatidylethanolamines (LPEs), in individuals with asthma and its mechanistic impact on epithelial cells and inflammatory cells as a model in vitro and in vivo. METHODS: Various cells were stimulated for intracellular calcium measurement and apoptosis assay. Degranulation was monitored by the release of b-hexosaminidase and the membrane perturbation was detected by fluorescent intensity of FM1-43. RESULTS: In a series of experimental observations, LPE18:1 and LPE22:6 were shown to be able to activate mast cells, macrophages and airway epithelial cells via their ability in causing membrane perturbation, increase in intracellular calcium, cytokines and, to certain degree, apoptosis, which could be reversed by the addition of albumin, but not oxidized albumin. Moreover, in a mouse model of airway inflammation, while, as expected, following antigen (OVA) sensitization and challenge, significant levels of inflammatory cells (eosinophils and neutrophils) were found in lung lavages, concomitant with elevated level of CCL1 chemokine, the co-exposure of IP (indeno[1,2,3-cd]pyrene) further enhanced these inflammatory parameters. Interestingly, significant elevation of LPE22:6 was noted in mice challenged with IP alone and in those OVAsensitized and challenged mice following the co-exposure with IP. CONCLUSIONS: LPE18:1 is bioactive with cell type-selective regulatory mechanisms and environmental pollutant exposure plays a critical role in the remodeling of phospholipids and the generation of its derivatives. |
