Nonpancreatic secretory phospholipase A2 (sPLA2) displays proinflammatory properties; however, its physiological substrate is not identified. Although inactive toward intact cells, sPLA2 hydrolyzed phospholipids in membrane microvesicles shed from Ca(2+)-loaded erythrocytes as well as from platelets and from whole blood cells challenged with inflammatory stimuli. sPLA2 was stimulated upon degradation of sphingomyelin (SPH) and produced lysophosphatidic acid (LPA), which induced platelet aggregation. Finally, lysophospholipid-containing vesicles and sPLA2 were detected in inflammatory fluids in relative proportions identical to those used in vitro. We conclude that upon loss of phospholipid asymmetry, cell-derived microvesicles provide a preferential substrate for sPLA2. SPH hydrolysis, which is provoked by various cytokines, regulates sPLA2 activity, and the novel lipid mediator LPA can be generated by this pathway.

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Sciences (grant no. UL1TR000039), and Arkansas Biosciences Institute (to R.C.K.). S.S.A has salary support from CEGIR (U54 AI117804) which is part of the Rare Diseases Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR), NCATS, and is funded through collaboration between NIAID, NIDDK, and NCATS, funded by AI114585 (to T.A.D.). Disclosure of potential conflict of interest: E. Tkachenko owns stock in MuWells Inc (supplier of elastic cell substrates

Atopic dermatitis (AD) is a multifactorial chronic inflammatory disease mainly stemming from a genetic predisposition that leads to hypersensitivity to environmental factors and a common involvement of Staphylococcus aureus (SA) colonization. The aim of this work was to propose a new non-invasive approach to enumerate the genes coding for the toxins of SA in atopic skin samples. In parallel, the study aimed to evaluate the change in AD through 3 markers of the inflammatory response: IL-8, IL-1RA/IL-1α and IL-18. These methods were tested on 31 patients with AD, and finally on a group of 19 subjects for whom clinical improvement had been reported after various treatments. The study revealed the presence of a large number of genes encoding toxins in atopic samples, indicating a high rate of SA colonization, and also an increase in the level of all cytokine markers in atopic skin compared to the skin of healthy subjects. Finally, we found a positive correlation between increases in the SCORAD (Scoring Atopic Dermatitis Index) value after treatment and the corresponding evolution of the SA density. These methods provide a means to clinically evaluate the course of AD, and may help in the development of potential treatments.