Michael H Gelb

University of Washington Seattle, Seattle, Washington, United States

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Publications (422)2435.22 Total impact

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    ABSTRACT: Oxidative stress and chronic low-grade inflammation in the lungs are associated with aging and may contribute to age-related immune dysfunction. To maintain lung homeostasis, chronic inflammation is countered by enhanced expression of proresolving/antiinflammatory factors. Here, we show that age-dependent increases of one such factor in the lungs, a phospholipase A2 (PLA2) group IID (PLA2G2D) with antiinflammatory properties, contributed to worse outcomes in mice infected with severe acute respiratory syndrome-coronavirus (SARS-CoV). Strikingly, infection of mice lacking PLA2G2D expression (Pla2g2d−/− mice) converted a uniformly lethal infection to a nonlethal one (>80% survival), subsequent to development of enhanced respiratory DC migration to the draining lymph nodes, augmented antivirus T cell responses, and diminished lung damage. We also observed similar effects in influenza A virus–infected middle-aged Pla2g2d−/− mice. Furthermore, oxidative stress, probably via lipid peroxidation, was fo
    Journal of Experimental Medicine 09/2015; DOI:10.1084/jem.20150632 · 12.52 Impact Factor
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    ABSTRACT: Background: There is interest in newborn screening and diagnosis of lysosomal storage diseases because of the development of treatment options that improve clinical outcome. Assays of lysosomal enzymes with high analytical range (ratio of assay response from the enzymatic reaction divided by the assay response due to nonenzymatic processes) are desirable because they are predicted to lead to a lower rate of false positives in population screening and to more accurate diagnoses. Methods: We designed new tandem mass spectrometry (MS/MS) assays that give the largest analytical ranges reported to date for the use of dried blood spots (DBS) for detection of mucopolysaccharidoses type II (MPS-II), MPS-IVA, and MPS-VI. For comparison, we carried out fluorometric assays of 6 lysosomal enzymes using 4-methylumbelliferyl (4MU)-substrate conjugates. Results: The MS/MS assays for MPS-II, -IVA, and -VI displayed analytical ranges that are nearly 2 orders of magnitude higher than those for the corresponding fluorometric assays. The relatively small analytical ranges of the 4MU assays are due to the intrinsic fluorescence of the 4MU substrates, which cause high background in the assay response. Conclusions: These highly reproducible MS/MS assays for MPS-II, -IVA, and -VI can support multiplex newborn screening of these lysosomal storage diseases. MS/MS assays of lysosomal enzymes outperform 4MU fluorometric assays in terms of analytical range. Ongoing pilot studies will allow us to gauge the impact of the increased analytical range on newborn screening performance.
    Clinical Chemistry 09/2015; DOI:10.1373/clinchem.2015.242560 · 7.91 Impact Factor
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    ABSTRACT: Treatments have been developed for mucopolysaccharidoses-IVA (MPS-IVA) and MPS-VI suggesting the need for eventual newborn screening. Biochemical enzyme assays are important for diagnosis. Previously reported fluorimetric assays of the relevant enzymes are based on substrates with poor activity or specificity. We developed new fluorimetric assays for N-acetylgalactosamine-6-sulfatase (GALNS) and arylsulfatase B (ARSB) based on the natural substrates, N-acetylgalactosamine-6-sulfate (and 4-sulfate), which have improved activity and specificity toward the relevant enzymes. The new substrates were tested on dried blood spots on newborn screening cards, and assays showed acceptable linearity in response with the amount of enzyme present (using quality control samples). When tested on dried blood spots from random newborns and affected patients, the assays showed good discrimination between the 2 sample groups. The analytical range of the new fluorimetric assays, defined as the ratio of enzyme-dependent-to-enzyme-independent assay response, is likely to be insufficient to use these assays for newborn screening. Rather, these new fluorimetric assays should be useful in a diagnostic lab to confirm a diagnosis via biochemical enzyme testing. Copyright © 2015. Published by Elsevier B.V.
    Clinica chimica acta; international journal of clinical chemistry 08/2015; DOI:10.1016/j.cca.2015.08.010 · 2.82 Impact Factor
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    ABSTRACT: Phospholipase A2s mediate the rate-limiting step in the formation of eicosanoids such as cysteinyl leukotrienes (CysLTs). Group IVA cytosolic PLA2α (cPLA2α) is thought to be the dominant PLA2 in eosinophils; however, eosinophils also have secreted PLA2 (sPLA2) activity that has not been fully defined. To examine the expression of sPLA2 group X (sPLA2-X) in eosinophils, the participation of sPLA2-X in the formation of CysLTs, and the mechanism by which sPLA2-X initiates the synthesis of CysLTs in eosinophils. Peripheral blood eosinophils were obtained from volunteers with asthma and/or allergy. A rabbit polyclonal anti-sPLA2-X antibody identified sPLA2-X by Western blot. We used confocal microscopy to colocalize the sPLA2-X to intracellular structures. An inhibitor of sPLA2-X (ROC-0929) that does not inhibit other mammalian sPLA2s, as well as inhibitors of the mitogen-activated kinase cascade (MAPK) and cPLA2α, was used to examine the mechanism of N-formyl-methionyl-leucyl-phenylalanine (fMLP)-mediated formation of CysLT. Eosinophils express the mammalian sPLA2-X gene (PLA2G10). The sPLA2-X protein is located in the endoplasmic reticulum, golgi, and granules of eosinophils and moves to the granules and lipid bodies during fMLP-mediated activation. Selective sPLA2-X inhibition attenuated the fMLP-mediated release of arachidonic acid and CysLT formation by eosinophils. Inhibitors of p38, extracellular-signal-regulated kinases 1/2 (p44/42 MAPK), c-Jun N-terminal kinase, and cPLA2α also attenuated the fMLP-mediated formation of CysLT. The sPLA2-X inhibitor reduced the phosphorylation of p38 and extracellular-signal-regulated kinases 1/2 (p44/42 MAPK) as well as cPLA2α during cellular activation, indicating that sPLA2-X is involved in activating the MAPK cascade leading to the formation of CysLT via cPLA2α. We further demonstrate that sPLA2-X is activated before secretion from the cell during activation. Short-term priming with IL-13 and TNF/IL-1β increased the expression of PLA2G10 by eosinophils. These results demonstrate that sPLA2-X plays a significant role in the formation of CysLTs by human eosinophils. The predominant role of the enzyme is the regulation of MAPK activation that leads to the phosphorylation of cPLA2α. The sPLA2-X protein is regulated by proteolytic cleavage, suggesting that an inflammatory environment may promote the formation of CysLTs through this mechanism. These results have important implications for the treatment of eosinophilic disorders such as asthma. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
    The Journal of allergy and clinical immunology 06/2015; DOI:10.1016/j.jaci.2015.05.026 · 11.48 Impact Factor
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    ABSTRACT: Platelets are anucleated blood elements highly potent at generating extracellular vesicles (EVs) called microparticles (MPs). Whereas EVs are accepted as an important means of intercellular communication, the mechanisms underlying platelet MP internalization in recipient cells are poorly understood. Our lipidomic analyses identified 12(S)-hydroxyeicosatetranoic acid [12(S)-HETE] as the predominant eicosanoid generated by MPs. Mechanistically, 12(S)-HETE is produced through the concerted activity of secreted phospholipase A2 IIA (sPLA2-IIA), present in inflammatory fluids, and platelet-type 12-lipoxygenase (12-LO), expressed by platelet MPs. Platelet MPs convey an elaborate set of transcription factors and nucleic acids, and contain mitochondria. We observed that MPs and their cargo are internalized by activated neutrophils in the endomembrane system via 12(S)-HETE. Platelet MPs are found inside neutrophils isolated from the joints of arthritic patients, and are found in neutrophils only in the presence of sPLA2-IIA and 12-LO in an in vivo model of autoimmune inflammatory arthritis. Using a combination of genetically modified mice, we show that the coordinated action of sPLA2-IIA and 12-LO promotes inflammatory arthritis. These findings identify 12(S)-HETE as a trigger of platelet MP internalization by neutrophils, a mechanism highly relevant to inflammatory processes. Because sPLA2-IIA is induced during inflammation, and 12-LO expression is restricted mainly to platelets, these observations demonstrate that platelet MPs promote their internalization in recipient cells through highly regulated mechanisms.
    Proceedings of the National Academy of Sciences 06/2015; 112(27). DOI:10.1073/pnas.1507905112 · 9.67 Impact Factor
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    ABSTRACT: The thymus is a primary lymphoid organ, home of maturation and selection of thymocytes for generation of functional T-cells. Multiple factors are involved throughout the different stages of the maturation process to tightly regulate T-cell production. The metabolism of arachidonic acid by cyclooxygenases, lipoxygenases and specific isomerases generates eicosanoids, lipid mediators capable of triggering cellular responses. In this study, we determined the profile of expression of the eicosanoids present in the mouse thymus at different stages of thymocyte development. As the group IVA cytosolic phospholipase A2 (cPLA2α) catalyzes the hydrolysis of phospholipids, thereby generating arachidonic acid, we further verified its contribution by including cPLA2α deficient mice to our investigations. We found that a vast array of eicosanoids is expressed in the thymus, which expression is substantially modulated through thymocyte development. The cPLA2α was dispensable in the generation of most eicosanoids in the thymus and consistently, the ablation of the cPLA2α gene in mouse thymus and the culture of thymuses from human newborns in presence of the cPLA2α inhibitor pyrrophenone did not impact thymocyte maturation. This study provides information on the eicosanoid repertoire present during thymocyte development and suggests that thymocyte maturation can occur independently of cPLA2α.
    PLoS ONE 05/2015; 10(5):e0126204. DOI:10.1371/journal.pone.0126204 · 3.23 Impact Factor
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    ABSTRACT: We have previously shown that secreted phospholipases A2 (sPLA2s) from animal venoms inhibit the in vitro development of P. falciparum, the agent of malaria. In addition, the inflammatory-type human group IIA (hGIIA) sPLA2 circulates at high levels in the serum of malaria patients. However, the role of the different human sPLA2s in host defense against P. falciparum has not been investigated. We show here that 4 out of 10 human sPLA2s, namely hGX, hGIIF, hGIII and hGV, exhibit potent in vitro anti-Plasmodium properties with IC50 values 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 sPLA2 catalytic activity and primarily due to hydrolysis of plasma lipoproteins from the parasite culture. Accordingly, purified lipoproteins that have been pre-hydrolyzed by hGX, hGIIF, hGIII and hGV are more toxic to P. falciparum than native lipoproteins. However, the total enzymatic activities of human sPLA2s 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 much less non-esterified fatty acids (NEFAs). Lipidomics analyses of released NEFAs from lipoproteins demonstrate that sPLA2s 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 sPLA2s were highly toxic, demonstrating the critical role of PUFAs. The selectivity of sPLA2s towards LDL and HDL lipoproteins and their ability to directly attack parasitized erythrocytes further explain their anti-Plasmodium activity. Together, our findings indicate that 4 human sPLA2s are active against P. falciparum in vitro and pave the way to future investigations on their in vivo contribution in malaria pathophysiology. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Infection and immunity 03/2015; 83(6). DOI:10.1128/IAI.02474-14 · 3.73 Impact Factor
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    ABSTRACT: Matrix metalloproteinase (MMP)-2 deficiency makes humans and mice susceptible to inflammation. Here, we reveal an MMP-2-mediated mechanism that modulates the inflammatory response via secretory phospholipase A2 (sPLA2), a phospholipid hydrolase that releases fatty acids, including precursors of eicosanoids. Mmp2(-/-) (and, to a lesser extent, Mmp7(-/-) and Mmp9(-/-)) mice had between 10- and 1000-fold elevated sPLA2 activity in plasma and heart, increased eicosanoids and inflammatory markers (both in the liver and heart), and exacerbated lipopolysaccharide-induced fever, all of which were blunted by adenovirus-mediated MMP-2 overexpression and varespladib (pharmacological sPLA2 inhibitor). Moreover, Mmp2 deficiency caused sPLA2-mediated dysregulation of cardiac lipid metabolic gene expression. Compared with liver, kidney, and skeletal muscle, the heart was the single major source of the Ca(2+)-dependent, ≈20-kDa, varespladib-inhibitable sPLA2 that circulates when MMP-2 is deficient. PLA2G5, which is a major cardiac sPLA2 isoform, was proinflammatory when Mmp2 was deficient. Treatment of wild-type (Mmp2(+/+)) mice with doxycycline (to inhibit MMP-2) recapitulated the Mmp2(-/-) phenotype of increased cardiac sPLA2 activity, prostaglandin E2 levels, and inflammatory gene expression. Treatment with either indomethacin (to inhibit cyclooxygenase-dependent eicosanoid production) or varespladib (which inhibited eicosanoid production) triggered acute hypertension in Mmp2(-/-) mice, revealing their reliance on eicosanoids for blood pressure homeostasis. A heart-centric MMP-2/sPLA2 axis may modulate blood pressure homeostasis, inflammatory and metabolic gene expression, and the severity of fever. This discovery helps researchers to understand the cardiovascular and systemic effects of MMP-2 inhibitors and suggests a disease mechanism for human MMP-2 gene deficiency. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
    Journal of the American Heart Association 03/2015; 4(4). DOI:10.1161/JAHA.115.001868 · 4.31 Impact Factor
  • Clinical Chemistry 03/2015; 61(5). DOI:10.1373/clinchem.2014.236448 · 7.91 Impact Factor
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    ABSTRACT: We describe a computationally designed enzyme, formolase (FLS), which catalyzes the carboligation of three one-carbon formaldehyde molecules into one three-carbon dihydroxyacetone molecule. The existence of FLS enables the design of a new carbon fixation pathway, the formolase pathway, consisting of a small number of thermodynamically favorable chemical transformations that convert formate into a three-carbon sugar in central metabolism. The formolase pathway is predicted to use carbon more efficiently and with less backward flux than any naturally occurring one-carbon assimilation pathway. When supplemented with enzymes carrying out the other steps in the pathway, FLS converts formate into dihydroxyacetone phosphate and other central metabolites in vitro. These results demonstrate how modern protein engineering and design tools can facilitate the construction of a completely new biosynthetic pathway.
    Proceedings of the National Academy of Sciences 03/2015; 112(12). DOI:10.1073/pnas.1500545112 · 9.67 Impact Factor
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    Molecular Genetics and Metabolism 02/2015; 114(2):S105-S106. DOI:10.1016/j.ymgme.2014.12.238 · 2.63 Impact Factor
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    ABSTRACT: Microparticles, also called microvesicles, are submicron extracellular vesicles produced by plasma membrane budding and shedding recognized as key actors in numerous physio(patho)logical processes. Since they can be released by virtually any cell lineages and are retrieved in biological fluids, microparticles appear as potent biomarkers. However, the small dimensions of microparticles and soluble factors present in body fluids can considerably impede their quantification. Here, flow cytometry with improved methodology for microparticle resolution was used to detect microparticles of human and mouse species generated from platelets, red blood cells, endothelial cells, apoptotic thymocytes and cells from the male reproductive tract. A family of soluble proteins, the secreted phospholipases A2 (sPLA2), comprises enzymes concomitantly expressed with microparticles in biological fluids and that catalyze the hydrolysis of membrane phospholipids. As sPLA2 can hydrolyze phosphatidylserine, a phospholipid frequently used to assess microparticles, and might even clear microparticles, we further considered the impact of relevant sPLA2 enzymes, sPLA2 group IIA, V and X, on microparticle quantification. We observed that if enriched in fluids, certain sPLA2 enzymes impair the quantification of microparticles depending on the species studied, the source of microparticles and the means of detection employed (surface phosphatidylserine or protein antigen detection). This study provides analytical considerations for appropriate interpretation of microparticle cytofluorometric measurements in biological samples containing sPLA2 enzymes.
    PLoS ONE 01/2015; 10(1):e0116812. DOI:10.1371/journal.pone.0116812 · 3.23 Impact Factor
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    ABSTRACT: Leishmaniasis is a parasitic disease and there are 20 different species. Newly introduced VL treatments, which include paromomycin, miltefosine, geographic extensions of liposomal amphotericin B, and various drug combinations, have substantially improved options for patients affected by visceral leishmaniasis (VL). This has been especially critical for treating VL cases in the state of Bihar, India, where resistance toward pentavalent antimonials is widely spread. However, in spite of this recent progress, new drugs for both leishmaniasis and Human African Trypanosomiasis (HAT) are still urgently needed. Treatment options for patients with VL in East Africa, HIV-VL coinfections, and those with post kala azar dermal leishmaniasis (PKDL) diagnosis are still inadequate, and new drugs that are inexpensive, orally bioavailable, short acting, and do not require hospitalization, would improve the treatment of VL patients in endemic areas. However, in spite of this recent progress, new drugs for both leishmaniasis and HAT are still urgently needed. There are only two compounds in clinical trials for HAT (nifurtimox, SCYX-7158) and one for VL (nifurtimox) making the need for enriching the pipeline with novel chemical entities of critical importance.
    Chemical Reviews 11/2014; 114(22). DOI:10.1021/cr500365f · 46.57 Impact Factor
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    ABSTRACT: Mitochondrial DNA (mtDNA) is a highly potent inflammatory trigger and is reportedly found outside the cells in blood in various pathologies. Platelets are abundant in blood where they promote hemostasis. While lacking a nucleus, platelets contain functional mitochondria. Upon activation, platelets produce extracellular vesicles known as microparticles. We hypothesized that activated platelets could also release their mitochondria. We show that activated platelets release respiratory-competent mitochondria, both within membrane-encapsulated microparticles and as free organelles. Extracellular mitochondria are found in platelet concentrates used for transfusion and are present at higher levels in those that induced acute reactions (febrile non-hemolytic reactions, skin manifestations and cardiovascular events) in transfused patients. We establish that the mitochondrion is an endogenous substrate of secreted phospholipase A2 IIA (sPLA2-IIA), a phospholipase otherwise specific for bacteria, likely reflecting the ancestral proteobacteria origin of mitochondria. The hydrolysis of the mitochondrial membrane by sPLA2-IIA yields inflammatory mediators (i.e. lysophospholipids, fatty acids and mtDNA) that promote leukocyte activation. Two-photon microscopy in live transfused-animals revealed that extracellular mitochondria interact with neutrophils in vivo, triggering neutrophil adhesion to the endothelial wall. Our findings identify extracellular mitochondria, produced by platelets, at the midpoint of a potent mechanism leading to inflammatory responses.
    Blood 07/2014; 124(14). DOI:10.1182/blood-2014-05-573543 · 10.45 Impact Factor
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    ABSTRACT: We report new substrates for quantitative enzyme activity measurements of human palmitoyl protein thioesterase (PPT1) and tripeptidyl peptidase (TPP1) in dried blood spots from newborns using tandem mass spectrometry. Deficiencies in these enzyme activities due to inborn errors of metabolism cause neuronal ceroid lipofuscinoses. The assays use synthetic compounds that were designed to mimic the natural substrates. Incubation produces nanomole quantities of enzymatic products per a blood spot that are quantified by tandem mass spectrometry using synthetic internal standards and selected reaction monitoring. The assays utilize a minimum steps for sample work up and can be run in a duplex format for the detection of neuronal ceroid lipofuscinoses or potentially multiplexed with other mass spectrometry-based assays for newborn screening of lysosomal storage disorders.
    Analytical Chemistry 07/2014; 86(15). DOI:10.1021/ac501994b · 5.64 Impact Factor
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    Michael H Gelb
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    ABSTRACT: This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
    Clinical Biochemistry 06/2014; DOI:10.1016/j.clinbiochem.2014.05.015 · 2.28 Impact Factor
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    ABSTRACT: Metabolic disorders, including obesity and insulin resistance, have their basis in dysregulated lipid metabolism and low-grade inflammation. In a microarray search of unique lipase-related genes whose expressions are associated with obesity, we found that two secreted phospholipase A2s (sPLA2s), PLA2G5 and PLA2G2E, were robustly induced in adipocytes of obese mice. Analyses of Pla2g5(-/-) and Pla2g2e(-/-) mice revealed distinct roles of these sPLA2s in diet-induced obesity. PLA2G5 hydrolyzed phosphatidylcholine in fat-overladen low-density lipoprotein to release unsaturated fatty acids, which prevented palmitate-induced M1 macrophage polarization. As such, PLA2G5 tipped the immune balance toward an M2 state, thereby counteracting adipose tissue inflammation, insulin resistance, hyperlipidemia, and obesity. PLA2G2E altered minor lipoprotein phospholipids, phosphatidylserine and phosphatidylethanolamine, and moderately facilitated lipid accumulation in adipose tissue and liver. Collectively, the identification of "metabolic sPLA2s" adds this gene family to a growing list of lipolytic enzymes that act as metabolic coordinators.
    Cell Metabolism 06/2014; DOI:10.1016/j.cmet.2014.05.002 · 17.57 Impact Factor
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    ABSTRACT: Tandem mass spectrometry for the multiplex and quantitative analysis of enzyme activities in dried blood spots on newborn screening cards has emerged as a powerful technique for early assessment of lysosomal storage diseases. Here we report the design and process-scale synthesis of substrates for the enzymes alpha-L-iduronidase, iduronate-2-sulfatase, and N-acetylgalactosamine-4-sulfatase that are used for newborn screening of mucopolysaccharidosis types I, II and VI. The products contain a bis-amide unit that is hypothesized to readily protonate in the gas phase, which improves detection sensitivity by tandem mass spectrometry. The products contain a benzoyl group, which provides a useful site for inexpensive deuteration, thus facilitating the preparation of internal standards for the accurate quantification of enzymatic products. Finally, the reagents are designed with ease of synthesis in mind, thus permitting scale up preparation to support worldwide newborn screening of lysosomal storage diseases. The new reagents provide the most sensitive assay for the 3 lysosomal enzymes reported to date as shown by their performance in reactions using dried blood spots as the enzyme source. Also, the ratio of assay signal to that measured in the absence of blood (background) is superior to all previously reported mucopolysaccharidosis types I, II an VI assays.
    Analytical Chemistry 04/2014; 86(9). DOI:10.1021/ac5004135 · 5.64 Impact Factor
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    ABSTRACT: The role of Group X secreted phospholipase A2 (GX-sPLA2) during influenza infection has not been previously investigated. We examined the role of GX-sPLA2 during H1N1 pandemic influenza infection in a GX-sPLA2 gene targeted mouse (GX−/−) model and found that survival after infection was significantly greater in GX−/− mice than in GX+/+ mice. Downstream products of GX-sPLA2 activity, PGD2, PGE2, LTB4, cysteinyl leukotrienes and Lipoxin A4 were significantly lower in GX−/− mice BAL fluid. Lung microarray analysis identified an earlier and more robust induction of T and B cell associated genes in GX−/− mice. Based on the central role of sPLA2 enzymes as key initiators of inflammatory processes, we propose that activation of GX-sPLA2 during H1N1pdm infection is an early step of pulmonary inflammation and its inhibition increases adaptive immunity and improves survival. Our findings suggest that GX-sPLA2 may be a potential therapeutic target during influenza.
    Virology 04/2014; s 454–455(1):78–92. DOI:10.1016/j.virol.2014.01.030 · 3.32 Impact Factor
  • Molecular Genetics and Metabolism 02/2014; 111(2):S22–S23. DOI:10.1016/j.ymgme.2013.12.033 · 2.63 Impact Factor

Publication Stats

22k Citations
2,435.22 Total Impact Points


  • 1970–2015
    • University of Washington Seattle
      • • Department of Chemistry
      • • Department of Biochemistry
      • • Department of Biological Structure
      Seattle, Washington, United States
  • 2000–2013
    • Showa University
      • Division of Health Chemistry
      Shinagawa, Tōkyō, Japan
  • 2012
    • University of Sfax
      Şafāqis, Şafāqis, Tunisia
  • 2011
    • University of Nice-Sophia Antipolis
      • Institut de Pharmacologie Moléculaire et Cellulaire (IPMC/UMR6097 CNRS-UNS)
      Valbonne, Provence-Alpes-Cote d'Azur, France
    • University of Toronto
      Toronto, Ontario, Canada
    • University of Kentucky
      • Graduate Center for Nutritional Sciences
      Lexington, Kentucky, United States
  • 2009
    • State University of New York Downstate Medical Center
      Brooklyn, New York, United States
  • 1990–2007
    • Howard Hughes Medical Institute
      Ashburn, Virginia, United States
    • University of Alberta
      • Department of Chemistry
      Edmonton, Alberta, Canada
  • 2005
    • City University of Seattle
      Seattle, Washington, United States
  • 2004
    • Cornell University
      • Department of Microbiology and Immunology
      Итак, New York, United States
  • 2003
    • University of Milan
      • Department of Pharmacological Sciences
      Milano, Lombardy, Italy
  • 2001
    • German Cancer Research Center
      Heidelburg, Baden-Württemberg, Germany
    • University of California, San Francisco
      • Department of Pharmaceutical Chemistry
      San Francisco, California, United States
  • 1989–1999
    • University of Delaware
      • Department of Chemistry and Biochemistry
      Ньюарк, Delaware, United States
  • 1995
    • Osaka City University
      • Department of Biochemistry
      Ōsaka, Ōsaka, Japan
  • 1993–1995
    • Swiss Institute for Art Research
      Zürich, Zurich, Switzerland
  • 1991–1992
    • Uppsala University
      Uppsala, Uppsala, Sweden
  • 1985–1986
    • Brandeis University
      Волтам, Massachusetts, United States