Phospholipidomic Profile Variation on THP-1 Cells Exposed to Skin or Respiratory Sensitizers and Respiratory Irritant

• Published in: Journal of cellular physiology 2016-12, Vol.231 (12), p.2639-2651
• Main Authors: Martins, João D., Maciel, Elisabete A., Silva, Ana, Ferreira, Isabel, Ricardo, Fernando, Domingues, Pedro, Neves, Bruno M., Domingues, Maria Rosário M., Cruz, Maria Teresa
• Format: Article
• Language: English
• Subjects: Allergies; Cell Line; Chemicals; Chromatography, Liquid; Chromatography, Thin Layer; Contact dermatitis; Dinitrofluorobenzene - pharmacology; Fatty Acids - metabolism; Humans; Hydrophobic and Hydrophilic Interactions; Irritants - pharmacology; Isocyanates - pharmacology; Lipid Peroxides - metabolism; Mass Spectrometry; Peroxidation; Phospholipids - metabolism; Principal Component Analysis; Real-Time Polymerase Chain Reaction; Relative abundance; Respiration - drug effects; RNA, Messenger - genetics; RNA, Messenger - metabolism; Salicylates - pharmacology; Skin - drug effects
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.25365

Occupational exposure to low molecular weight reactive chemicals often leads to development of allergic reactions such as allergic contact dermatitis and respiratory allergies. Further insights into the interaction of these chemicals with physiopathological relevant cellular models might provide the foundations for novel non‐animal approaches to safety assessment. In this work we used the human THP‐1 cell line to determine phospholipidome changes induced by the skin sensitizer 1‐fluoro‐2,4‐dinitrobenzene (DNFB), the respiratory allergen hexamethylene diisocyanate (HDI), and the irritant methyl salicylate (MESA). We detected that these chemicals differently induce lipid peroxidation and modulate THP‐1 IL‐1β, IL‐12B, IL‐8, CD86, and HMOX1 transcription. Decreased phosphatidylethanolamine content was detected in cells exposed to MESA, while profound alterations in the relative abundance of cardiolipin species were observed in cells exposed to DNFB. All chemicals tested induced a decrease in the relative abundance of plasmanyl phosphatidylcholine species PC (O‐16:0e/18:1) and phosphatidylinositol species PI (34:1), while increasing PI (38:4). An increased abundance of oleic acid was observed in the phospholipids of cells exposed to DNFB while a decreased abundance of palmitic acid was detected in cells treated with MESA or DNFB. We conclude that both specific and common alterations at phospholipidome levels are triggered by the different chemicals, while not allowing a complete distinction between them using a Canonical Analysis of Principal Coordinates (CAP). The common effects observed at phospholipids level with all the chemicals tested might be related to unspecific cell cytotoxic mechanisms that nevertheless may contribute to the elicitation of specific immune responses. J. Cell. Physiol. 231: 2639–2651, 2016. © 2016 Wiley Periodicals, Inc. The skin sensitizer 1‐fluoro‐2,4‐dinitrobenzene (DNFB), the respiratory allergen hexamethylene diisocyanate (HDI), and the irritant methyl salicylate (MESA) trigger both specific and common alterations at THP‐1 phospholipidome level. To some extent these alterations are dependent on the oxidative capacity of the chemicals and may be important in shaping THP‐1 cells’ maturation.