LysoPC and PAF Trigger Arachidonic Acid Release by Divergent Signaling Mechanisms in Monocytes

Overview

Journal J Lipids

Publisher Wiley

Date 2011 Sep 14

PMID 21912747

Citations 23

Authors

Janne Oestvang

Marit W Anthonsen

Berit Johansen

Affiliations

Soon will be listed here.

Abstract

Oxidized low-density lipoproteins (LDLs) play an important role during the development of atherosclerosis characterized by intimal inflammation and macrophage accumulation. A key component of LDL is lysophosphatidylcholine (lysoPC). LysoPC is a strong proinflammatory mediator, and its mechanism is uncertain, but it has been suggested to be mediated via the platelet activating factor (PAF) receptor. Here, we report that PAF triggers a pertussis toxin- (PTX-) sensitive intracellular signaling pathway leading to sequential activation of sPLA(2), PLD, cPLA(2), and AA release in human-derived monocytes. In contrast, lysoPC initiates two signaling pathways, one sequentially activating PLD and cPLA(2), and a second parallel PTX-sensitive pathway activating cPLA(2) with concomitant activation of sPLA(2), all leading to AA release. In conclusion, lysoPC and PAF stimulate AA release by divergent pathways suggesting involvement of independent receptors. Elucidation of monocyte lysoPC-specific signaling mechanisms will aid in the development of novel strategies for atherosclerosis prevention, diagnosis, and therapy.

Citing Articles

A global lipid map of severe fever with thrombocytopenia syndrome virus infection reveals glycerophospholipids as novel prognosis biomarkers.

Tian P, Zhao L, Zhang G, Chen S, Zhang W, Ou M mBio. 2024; 15(12):e0262824.

PMID: 39535228 PMC: 11633121. DOI: 10.1128/mbio.02628-24.

Specific microRNA Profile Associated with Inflammation and Lipid Metabolism for Stratifying Allergic Asthma Severity.

Escolar-Pena A, Delgado-Dolset M, Pablo-Torres C, Tarin C, Mera-Berriatua L, Cuesta Apausa M Int J Mol Sci. 2024; 25(17).

PMID: 39273372 PMC: 11394998. DOI: 10.3390/ijms25179425.

Ocrelizumab alters the circulating metabolome in people with relapsing-remitting multiple sclerosis.

Siavoshi F, Ladakis D, Muller A, Nourbakhsh B, Bhargava P Ann Clin Transl Neurol. 2024; 11(9):2485-2498.

PMID: 39185939 PMC: 11537130. DOI: 10.1002/acn3.52167.

TET1 displays catalytic and non-catalytic functions in the adult mouse cortex.

Foong Y, Caldwell B, Thorvaldsen J, Krapp C, Mesaros C, Zhou W Epigenetics. 2024; 19(1):2374979.

PMID: 38970823 PMC: 11229741. DOI: 10.1080/15592294.2024.2374979.

The Role of Lysophospholipid Metabolites LPC and LPA in the Pathogenesis of Chronic Obstructive Pulmonary Disease.

Zhou Q, Chen Y, Liang Y, Sun Y Metabolites. 2024; 14(6).

PMID: 38921452 PMC: 11205356. DOI: 10.3390/metabo14060317.

References

Hashimoto S, Matsumoto K, Gon Y, Maruoka S, Kujime K, Hayashi S . p38 MAP kinase regulates TNF alpha-, IL-1 alpha- and PAF-induced RANTES and GM-CSF production by human bronchial epithelial cells. Clin Exp Allergy. 1999; 30(1):48-55. DOI: 10.1046/j.1365-2222.2000.00641.x. View

Meats J, Steele L, Bowen J . Identification of phospholipase D (PLD) activity in mouse peritoneal macrophages. Agents Actions. 1993; 39 Spec No:C14-6. DOI: 10.1007/BF01972706. View

Grigoriadis G, Stewart A . Albumin inhibits platelet-activating factor (PAF)-induced responses in platelets and macrophages: implications for the biologically active form of PAF. Br J Pharmacol. 1992; 107(1):73-7. PMC: 1907628. DOI: 10.1111/j.1476-5381.1992.tb14465.x. View

Heuer H . Use of WEB 2086 and WEB 2170 as platelet-activating factor antagonists. Methods Enzymol. 1990; 187:455-65. DOI: 10.1016/0076-6879(90)87052-5. View

Anthonsen M, Andersen S, Solhaug A, Johansen B . Atypical lambda/iota PKC conveys 5-lipoxygenase/leukotriene B4-mediated cross-talk between phospholipase A2s regulating NF-kappa B activation in response to tumor necrosis factor-alpha and interleukin-1beta. J Biol Chem. 2001; 276(38):35344-51. DOI: 10.1074/jbc.M105264200. View

Ishii S, Shimizu T . Platelet-activating factor (PAF) receptor and genetically engineered PAF receptor mutant mice. Prog Lipid Res. 2000; 39(1):41-82. DOI: 10.1016/s0163-7827(99)00016-8. View

Hefner Y, Murakami M, Wilde J, Pasquet S, Schieltz D, Ghomashchi F . Serine 727 phosphorylation and activation of cytosolic phospholipase A2 by MNK1-related protein kinases. J Biol Chem. 2000; 275(48):37542-51. DOI: 10.1074/jbc.M003395200. View

Locati M, Riboldi E, Bonecchi R, Transidico P, Bernasconi S, Haribabu B . Selective induction of phospholipase D1 in pathogen-activated human monocytes. Biochem J. 2001; 358(Pt 1):119-25. PMC: 1222039. DOI: 10.1042/0264-6021:3580119. View

Lin P, Ye R . The lysophospholipid receptor G2A activates a specific combination of G proteins and promotes apoptosis. J Biol Chem. 2003; 278(16):14379-86. DOI: 10.1074/jbc.M209101200. View

10.

Wang L, Radu C, Yang L, Bentolila L, Riedinger M, Witte O . Lysophosphatidylcholine-induced surface redistribution regulates signaling of the murine G protein-coupled receptor G2A. Mol Biol Cell. 2005; 16(5):2234-47. PMC: 1087231. DOI: 10.1091/mbc.e04-12-1044. View

11.

Kabarowski J, Zhu K, Le L, Witte O, Xu Y . Lysophosphatidylcholine as a ligand for the immunoregulatory receptor G2A. Science. 2001; 293(5530):702-5. DOI: 10.1126/science.1061781. View

12.

Balboa M, Balsinde J, Dennis E . Involvement of phosphatidate phosphohydrolase in arachidonic acid mobilization in human amnionic WISH cells. J Biol Chem. 1998; 273(13):7684-90. DOI: 10.1074/jbc.273.13.7684. View

13.

Jing Q, Xin S, Zhang W, Wang P, Qin Y, Pei G . Lysophosphatidylcholine activates p38 and p42/44 mitogen-activated protein kinases in monocytic THP-1 cells, but only p38 activation is involved in its stimulated chemotaxis. Circ Res. 2000; 87(1):52-9. DOI: 10.1161/01.res.87.1.52. View

14.

Chao W, Liu H, HANAHAN D, Olson M . Regulation of platelet-activating factor receptor and PAF receptor-mediated arachidonic acid release by protein kinase C activation in rat Kupffer cells. Arch Biochem Biophys. 1990; 282(1):188-97. DOI: 10.1016/0003-9861(90)90103-6. View

15.

BLIGH E, Dyer W . A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959; 37(8):911-7. DOI: 10.1139/o59-099. View

16.

Glaser K, Asmis R, Dennis E . Bacterial lipopolysaccharide priming of P388D1 macrophage-like cells for enhanced arachidonic acid metabolism. Platelet-activating factor receptor activation and regulation of phospholipase A2. J Biol Chem. 1990; 265(15):8658-64. View

17.

Yang L, Radu C, Wang L, Riedinger M, Witte O . Gi-independent macrophage chemotaxis to lysophosphatidylcholine via the immunoregulatory GPCR G2A. Blood. 2004; 105(3):1127-34. DOI: 10.1182/blood-2004-05-1916. View

18.

Oestvang J, Anthonsen M, Johansen B . Role of secretory and cytosolic phospholipase A(2) enzymes in lysophosphatidylcholine-stimulated monocyte arachidonic acid release. FEBS Lett. 2003; 555(2):257-62. DOI: 10.1016/s0014-5793(03)01242-0. View

19.

Andersen S, Sjursen W, Laegreid A, Volden G, Johansen B . Elevated expression of human nonpancreatic phospholipase A2 in psoriatic tissue. Inflammation. 1994; 18(1):1-12. DOI: 10.1007/BF01534593. View

20.

Ueno N, Murakami M, Kudo I . Functional crosstalk between phospholipase D(2) and signaling phospholipase A(2)/cyclooxygenase-2-mediated prostaglandin biosynthetic pathways. FEBS Lett. 2000; 475(3):242-6. DOI: 10.1016/s0014-5793(00)01691-4. View