scholarly journals Lipid Profile of Activated Macrophages and Contribution of Group V Phospholipase A2

Biomolecules ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 25
Author(s):  
Masaya Koganesawa ◽  
Munehiro Yamaguchi ◽  
Sachin K. Samuchiwal ◽  
Barbara Balestrieri

Macrophages activated by Interleukin (IL)-4 (M2) or LPS+ Interferon (IFN)γ (M1) perform specific functions respectively in type 2 inflammation and killing of pathogens. Group V phospholipase A2 (Pla2g5) is required for the development and functions of IL-4-activated macrophages and phagocytosis of pathogens. Pla2g5-generated bioactive lipids, including lysophospholipids (LysoPLs), fatty acids (FAs), and eicosanoids, have a role in many diseases. However, little is known about their production by differentially activated macrophages. We performed an unbiased mass-spectrometry analysis of phospholipids (PLs), LysoPLs, FAs, and eicosanoids produced by Wild Type (WT) and Pla2g5-null IL-4-activated bone marrow-derived macrophages (IL-4)BM-Macs (M2) and (LPS+IFNγ)BM-Macs (M1). Phosphatidylcholine (PC) was preferentially metabolized in (LPS+IFNγ)BM-Macs and Phosphatidylethanolamine (PE) in (IL-4)BM-Macs, with Pla2g5 contributing mostly to metabolization of selected PE molecules. While Pla2g5 produced palmitic acid (PA) in (LPS+IFNγ)BM-Macs, the absence of Pla2g5 increased myristic acid (MA) in (IL-4)BM-Macs. Among eicosanoids, Prostaglandin E2 (PGE2) and prostaglandin D2 (PGD2) were significantly reduced in (IL-4)BM-Macs and (LPS+IFNγ)BM-Macs lacking Pla2g5. Instead, the IL-4-induced increase in 20-carboxy arachidonic acid (20CooH AA) was dependent on Pla2g5, as was the production of 12-hydroxy-heptadecatrienoic acid (12-HHTrE) in (LPS+IFNγ)BM-Macs. Thus, Pla2g5 contributes to PE metabolization, PGE2 and PGD2 production independently of the type of activation, while in (IL-4)BM-Macs, Pla2g5 regulates selective lipid pathways and likely novel functions.

2020 ◽  
Vol 11 ◽  
pp. 204062232092415
Author(s):  
Alexandra E. Butler ◽  
Soha R. Dargham ◽  
Aishah Latif ◽  
Haira R. Mokhtar ◽  
Amal Robay ◽  
...  

Background: Epidemiological studies have suggested that vitamin D deficiency is associated with the development of type 2 diabetes (T2DM) and is related to diabetes complications. This study was undertaken to determine the relationship between diabetes complications and cardiovascular risk factors with vitamin D3 and its metabolites: 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), 25-hydroxyvitamin D3 (25(OH)D3), 24,25-dihydroxyvitamin D3 (24,25(OH)2D3); and 25-hydroxy-3epi-vitamin D3 (3epi25(OH)D3). Methods: 750 Qatari subjects, 460 (61.3%) with and 290 (38.7%) without T2DM, who were not taking vitamin D3 supplements, participated in this cross-sectional, observational study. Plasma concentrations of vitamin D3 and its metabolites were measured by liquid chromatography tandem mass spectrometry analysis. Results: T2DM subjects had lower concentrations of all vitamin D3 metabolites ( p < 0.001) except 3epi25(OH)D3 ( p < 0.071). Males had higher concentrations of all vitamin D3 metabolites ( p < 0.001). In the T2DM subjects, lower 25(OH)D3 was associated with retinopathy ( p < 0.03) and dyslipidemia ( p < 0.04), but not neuropathy or vascular complications; lower 1,25(OH)2D3 was associated with hypertension ( p < 0.009), dyslipidemia ( p < 0.003) and retinopathy ( p < 0.006), and coronary artery disease ( p < 0.012), but not neuropathy; lower 24,25(OH)2D3 concentrations were associated with dyslipidemia alone ( p < 0.019); 3epi25(OH)D3 associated with diabetic neuropathy alone ( p < 0.029). In nondiabetics, 25(OH)D3, 1,25(OH)2D3 and 24,25(OH)2D3 were associated with dyslipidemia ( p < 0.001, p < 0.001, p < 0.015, respectively) and lower 1,25(OH)2D3 was associated with hypertension ( p < 0.001). Spearman’s correlation showed 1,25(OH)2D3 to be negatively correlated to age and diabetes duration. Conclusions: Different diabetes complications were associated with differing vitamin D parameters, with diabetic retinopathy related to lower 25(OH)D3 and 1,25(OH)2D3 levels, hypertension significantly associated with lower 1,25(OH)2D3, while dyslipidemia was associated with lower 25(OH)D3, 1,25(OH)2D3 and 24,25(OH)2D3. While 25(OH)D metabolites were lower in females, there was not an exaggeration in complications.


2013 ◽  
Vol 81 (10) ◽  
pp. 3793-3802 ◽  
Author(s):  
Rodrigo T. Hernandes ◽  
Miguel A. De la Cruz ◽  
Denise Yamamoto ◽  
Jorge A. Girón ◽  
Tânia A. T. Gomes

ABSTRACTAtypical enteropathogenicEscherichia coli(aEPEC) strains are diarrheal pathogens that lack bundle-forming pilus production but possess the virulence-associated locus of enterocyte effacement. aEPEC strain 1551-2 produces localized adherence (LA) on HeLa cells; however, its isogenic intimin (eae) mutant produces a diffuse-adherence (DA) pattern. In this study, we aimed to identify the DA-associated adhesin of the 1551-2eaemutant. Electron microscopy of 1551-2 identified rigid rod-like pili composed of an 18-kDa protein, which was identified as the major pilin subunit of type 1 pilus (T1P) by mass spectrometry analysis. Deletion offimAin 1551-2 affected biofilm formation but had no effect on adherence properties. Analysis of secreted proteins in supernatants of this strain identified a 150-kDa protein corresponding to SslE, a type 2 secreted protein that was recently reported to be involved in biofilm formation of rabbit and human EPEC strains. However, neither adherence nor biofilm formation was affected in a 1551-2sslEmutant. We then investigated the role of the EspA filament associated with the type 3 secretion system (T3SS) in DA by generating a doubleeae espAmutant. This strain was no longer adherent, strongly suggesting that the T3SS translocon is the DA adhesin. In agreement with these results, specific anti-EspA antibodies blocked adherence of the 1551-2eaemutant. Our data support a role for intimin in LA, for the T3SS translocon in DA, and for T1P in biofilm formation, all of which may act in concert to facilitate host intestinal colonization by aEPEC strains.


Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 152
Author(s):  
Barbara Balestrieri ◽  
David Di Costanzo ◽  
Daniel F. Dwyer

Macrophages have diverse functions in the pathogenesis, resolution, and repair of inflammatory processes. Elegant studies have elucidated the metabolomic and transcriptomic profiles of activated macrophages. However, the versatility of macrophage responses in inflammation is likely due, at least in part, to their ability to rearrange their repertoire of bioactive lipids, including fatty acids and oxylipins. This review will describe the fatty acids and oxylipins generated by macrophages and their role in type 1 and type 2 immune responses. We will highlight lipidomic studies that have shaped the current understanding of the role of lipids in macrophage polarization.


2015 ◽  
Vol 44 (36) ◽  
pp. 15813-15822 ◽  
Author(s):  
P. I. Molina ◽  
D. J. Sures ◽  
P. Miró ◽  
L. N. Zakharov ◽  
M. Nyman

Reaction of Ta peroxometalate and tungstate affords the first systematic series of Ta/W isopolyoxometalates. An analogous reaction system yields a Nb/W cluster. The electronic structure and stability of these clusters varies as a function of the group V metal content, as inferred from spectroscopic, electrochemical and mass-spectrometry analysis and confirmed by DFT calculations.


2012 ◽  
Vol 53 ◽  
pp. S213-S214 ◽  
Author(s):  
S. Pasha⁎ ◽  
A.K. Mahalka ◽  
A. Reis ◽  
A.R. Pitt ◽  
P.K.J. Kinnunen ◽  
...  

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