Group V Phospholipase A2 in Bone Marrow-derived Myeloid Cells and Bronchial Epithelial Cells Promotes Bacterial Clearance after Escherichia coli Pneumonia

Dégousée, Norbert; Kelvin, David J.; Geißlinger, Gerd; Hwang, David; Stefanski, Eva; Wang, Xing Hua; Danesh, Ali; Angioni, Carlo; Schmidt, Helmut; Lindsay, Thomas F.; Gelb, Michael H.; Bollinger, James G.; Payré, Christine; Lambeau, Gérard; Jonathan, P.; Keating, Armand; Rubin, Barry B.

doi:10.1074/jbc.m111.262733

Cited by 22 publications

(18 citation statements)

References 52 publications

(71 reference statements)

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“…In the process of Th2-dependent asthma, sPLA 2 -V appears to function in antigen-presenting cells to regulate antigen processing and thereby the Th2 response, as well as in airway epithelial cells to promote airway injury that may involve surfactant degradation ( 34,92,94,95 ). In contrast, Pla2g5 Ϫ / Ϫ mice are more susceptible to Candida albicans or Escherichia coli infection (Th1 immunity) and arthritis (Th17 immunity) accompanied by reduced clearance of harmful materials (microorganisms and immune complex, respectively) by macrophages ( 63,96,97 ). As M2 macrophages have greater phagocytic activity, the reduced phagocytosis in Pla2g5 Ϫ / Ϫ macrophages could also be partly explained by the ability of sPLA 2 -V to promote M2 macrophage polarization in Th2 immunity and therefore to counteract Th1/Th17 immunity.…”

Section: S Participate In Diverse Biologicalmentioning

confidence: 99%

A new era of secreted phospholipase A2

Murakami

Sato

Miki

et al. 2015

Journal of Lipid Research

204

170

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More than one third of the phospholipase A 2 (PLA 2 ) enzymes belong to the secreted PLA 2 (sPLA 2 ) family, which contains 10 catalytically active isoforms (IB, IIA, IIC, IID, IIE, IIF, III, V, X, and XIIA) and one inactive isoform (XIIB) in mammals ( 1-4 ). Individual sPLA 2 s exhibit unique tissue and cellular distributions and substrate selectivity, suggesting their distinct biological roles. Because sPLA 2 s are secreted and require millimolar Ca 2+ for their catalytic action, they principally target phospholipids in the extracellular space. Individual sPLA 2 s participate in diverse biological This work was supported by

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Section: S Participate In Diverse Biologicalmentioning

confidence: 99%

A new era of secreted phospholipase A2

Murakami

Sato

Miki

et al. 2015

Journal of Lipid Research

204

170

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“…We have combined the bacteria-induced pneumonia model, which represents one of the most frequent human infectious diseases (20, 21) or LPS-induced ALI model (22) with an experimental tumor lung metastasis model to study the effect of acute inflammation in the same metastatic microenvironment, with multiple cancer types tested. The critical role of the CXCR4 axis in the enhanced lung metastasis effect was investigated using pharmacological inhibitors, a neutralizing antibody, and genetic forms of signaling molecules.…”

Section: Introductionmentioning

confidence: 99%

The Ubiquitin–CXCR4 Axis Plays an Important Role in Acute Lung Infection–Enhanced Lung Tumor Metastasis

Yan

Cai

2013

Clinical Cancer Research

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Purpose Our goals are to test the effect of acute lung infection on tumor metastasis and to investigate the underlying mechanisms. Experimental Design We combined bacteria- and lipopolysaccharide (LPS)-induced acute lung injury/inflammation (ALI) mouse models with mouse metastatic models to study the effect of acute inflammation on lung metastasis in mice. The mechanisms were invested in ex vivo, in vitro, and in vivo studies. Results Both bacteria- and LPS-induced acute lung injury/inflammation significantly enhanced lung metastasis of four tail vein-injected mouse tumor cell lines. Bacteria also enhanced lung metastasis when 4T1 cells orthotopically injected. The broncheoalveolar lavage fluid (BALF) from LPS- or bacteria- injected mice stimulated migration of tumor cells. In vivo tracking of metastatic RM-9 cells showed that bacterial injection enhanced early dissemination of tumor cells to the lung. The majority of the BALF migratory activity could be blocked by AMD3100, a CXCR4 inhibitor. All tested cell lines expressed CXCR4. The levels of extracellular ubiquitin (Ub), but not SDF-1, in BALF were significantly increased by LPS. Ub was able to induce AMD3100-sensitive migration of tumor cells. Finally, the anti-bacterial amoxicillin and AMD3100 blocked the enhancement effect of bacterial infection on tumor metastasis. Conclusions Acute lung infection dramatically increased cancer cell homing to the lung and lung metastasis. This may be due to an alteration of the lung microenvironment and preparation of a favorable metastatic “niche”. This effect was seen in multiple cancer types and thus may have broad applications for cancer patients in prevention and/or treatment of metastasis.

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“…Human sPLA 2 s exhibit different enzymatic properties (11) as well as unique tissue and cellular distributions (10), suggesting distinct physiological roles for each enzyme. Besides their role in lipid mediator production, accumulating evidence indicates that sPLA 2 s participate in innate immunity, especially in the first line of host defense against bacteria and other pathogens (12)(13)(14)(15)(16)(17)(18)(19)(20)(21).…”

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confidence: 99%

In Vitro Anti-Plasmodium falciparum Properties of the Full Set of Human Secreted Phospholipases A ₂

et al. 2015

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We have previously shown that secreted phospholipases A 2 (sPLA 2 s) from animal venoms inhibit the in vitro development of Plasmodium falciparum, the agent of malaria. In addition, the inflammatory-type human group IIA (hGIIA) sPLA 2 circulates at high levels in the serum of malaria patients. However, the role of the different human sPLA 2 s in host defense against P. falciparum has not been investigated. We show here that 4 out of 10 human sPLA 2 s, namely, hGX, hGIIF, hGIII, and hGV, exhibit potent in vitro anti-Plasmodium properties with half-maximal inhibitory concentrations (IC 50 s) of 2.9 ؎ 2.4, 10.7 ؎ 2.1, 16.5 ؎ 9.7, and 94.2 ؎ 41.9 nM, respectively. Other human sPLA2s, including hGIIA, are inactive. The inhibition is dependent on sPLA 2 catalytic activity and primarily due to hydrolysis of plasma lipoproteins from the parasite culture. Accordingly, purified lipoproteins that have been prehydrolyzed by hGX, hGIIF, hGIII, and hGV are more toxic to P. falciparum than native lipoproteins. However, the total enzymatic activities of human sPLA 2 s on purified lipoproteins or plasma did not reflect their inhibitory activities on P. falciparum. For instance, hGIIF is 9-fold more toxic than hGV but releases a lower quantity of nonesterified fatty acids (NEFAs). Lipidomic analyses of released NEFAs from lipoproteins demonstrate that sPLA 2 s with anti-Plasmodium properties are those that release polyunsaturated fatty acids (PUFAs), with hGIIF being the most selective enzyme. NEFAs purified from lipoproteins hydrolyzed by hGIIF were more potent at inhibiting P. falciparum than those from hGV, and PUFA-enriched liposomes hydrolyzed by sPLA 2 s were highly toxic, demonstrating the critical role of PUFAs. The selectivity of sPLA 2 s toward lowand high-density (LDL and HDL, respectively) lipoproteins and their ability to directly attack parasitized erythrocytes further explain their anti-Plasmodium activity. Together, our findings indicate that 4 human sPLA 2 s are active against P. falciparum in vitro and pave the way to future investigations on their in vivo contribution in malaria pathophysiology.

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Group V Phospholipase A2 in Bone Marrow-derived Myeloid Cells and Bronchial Epithelial Cells Promotes Bacterial Clearance after Escherichia coli Pneumonia

Cited by 22 publications

References 52 publications

A new era of secreted phospholipase A2

A new era of secreted phospholipase A2

The Ubiquitin–CXCR4 Axis Plays an Important Role in Acute Lung Infection–Enhanced Lung Tumor Metastasis

In Vitro Anti-Plasmodium falciparum Properties of the Full Set of Human Secreted Phospholipases A ₂

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Group V Phospholipase A2 in Bone Marrow-derived Myeloid Cells and Bronchial Epithelial Cells Promotes Bacterial Clearance after Escherichia coli Pneumonia

Cited by 22 publications

References 52 publications

A new era of secreted phospholipase A2

A new era of secreted phospholipase A2

The Ubiquitin–CXCR4 Axis Plays an Important Role in Acute Lung Infection–Enhanced Lung Tumor Metastasis

In Vitro Anti-Plasmodium falciparum Properties of the Full Set of Human Secreted Phospholipases A 2

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In Vitro Anti-Plasmodium falciparum Properties of the Full Set of Human Secreted Phospholipases A ₂