UM
Lysophosphatidylcholine modulates neutrophil oxidant production through elevation of cyclic AMP
Lin P.1; Welch E.J.1; Gao X.-P.1; Malik A.B.1; Ye R.D.1
2005-03-01
Source PublicationJournal of Immunology
ISSN00221767
Volume174Issue:5Pages:2981-2989
AbstractLysophosphatidylcholine (LPC) is an oxidized phospholipid present in micromolar concentrations in blood and inflamed tissues. The effects of LPC on neutrophil functions remain incompletely understood, because conflicting reports exist for its stimulatory and inhibitory roles. We report in this study that LPC inhibits superoxide generation in fMLP- and PMA-stimulated neutrophils without affecting fMLP-induced Ca mobilization and cell viability. This effect was observed with LPC dissolved in ethanol, but not with LPC stock solutions prepared in water or in BSA-containing aqueous solution with sonication. Under the same experimental conditions, platelet-activating factor primed neutrophils for superoxide generation. The inhibitory effect of LPC was observed within 30 s after its application and was maximal at LPC concentrations between 0.1 and 1 μM. Inhibition of superoxide generation was accompanied by a 2.5-fold increase in the intracellular cAMP concentration. In addition, LPC reduced fMLP-stimulated phosphorylation of ERK and Akt and membrane translocation of p67 and p47. The protein kinase A inhibitors H-89 and adenosine 3′5′-cyclic monophosphorothioate Rp-isomer (Rp-cAMP) partially restored superoxide production in LPC-treated neutrophils, indicating involvement of protein kinase A in LPC-mediated inhibition. Using an ex vivo mouse lung perfusion model that measures lung weight change and capillary filtration coefficient, we found that LPC prevented lung vascular injury mediated by fMLP-activated neutrophils. Taken together, these results suggest that LPC-induced elevation of intracellular cAMP is partially responsible for its inhibition of neutrophil NADPH oxidase activation. A similar mechanism of inhibition may be used for the control of neutrophil-mediated tissue injury.
DOI10.4049/jimmunol.174.5.2981
URLView the original
Language英語
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Cited Times [WOS]:58   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.University of Illinois College of Medicine
2.University of Illinois at Chicago
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Lin P.,Welch E.J.,Gao X.-P.,et al. Lysophosphatidylcholine modulates neutrophil oxidant production through elevation of cyclic AMP[J]. Journal of Immunology,2005,174(5):2981-2989.
APA Lin P.,Welch E.J.,Gao X.-P.,Malik A.B.,&Ye R.D..(2005).Lysophosphatidylcholine modulates neutrophil oxidant production through elevation of cyclic AMP.Journal of Immunology,174(5),2981-2989.
MLA Lin P.,et al."Lysophosphatidylcholine modulates neutrophil oxidant production through elevation of cyclic AMP".Journal of Immunology 174.5(2005):2981-2989.
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