All Title Author
Keywords Abstract


Lysophosphatidylcholine: A Novel Modulator of Trypanosoma cruzi Transmission

DOI: 10.1155/2012/625838

Full-Text   Cite this paper   Add to My Lib

Abstract:

Lysophosphatidylcholine is a bioactive lipid that regulates a large number of cellular processes and is especially present during the deposition and infiltration of inflammatory cells and deposition of atheromatous plaque. Such molecule is also present in saliva and feces of the hematophagous organism Rhodnius prolixus, a triatominae bug vector of Chagas disease. We have recently demonstrated that LPC is a modulator of Trypanosoma cruzi transmission. It acts as a powerful chemoattractant for inflammatory cells at the site of the insect bite, which will provide a concentrated population of cells available for parasite infection. Also, LPC increases macrophage intracellular calcium concentrations that ultimately enhance parasite invasion. Finally, LPC inhibits NO production by macrophages stimulated by live T. cruzi, and thus interferes with the immune system of the vertebrate host. In the present paper, we discuss the main signaling mechanisms that are likely used by such molecule and their eventual use as targets to block parasite transmission and the pathogenesis of Chagas disease. 1. Immune Response to Trypanosoma cruzi Infection in the Vertebrate Host T. cruzi infects the vertebrate host through bite wounds produced in skin by a feeding bug or through the interaction of the parasite with conjunctival mucosa. Such interaction sometimes produces visible signs called Roma?a’s sign or chagoma inoculation. The histology of this initial site of infection is defined by an elevated number of mononuclear cells [1]. This first sign of infection suggests that T. cruzi can stimulate skin cells to produce mediators that trigger a local inflammatory response. Despite controversies about the mechanism of the pathogenesis of Chagas disease [2–5], until recently, some authors believed that the disease was limited to an acute phase, followed by a chronic phase that was considered an autoimmune disease, where the parasites would be physically linked to sites of inflammation in the heart and esophagus [6–8]. However, nowadays, the disease is considered multifactorial, with multiple and continuous interactions between pathogen and host [9]. After the incubation period of 2 to 3 weeks, infection with T. cruzi is manifested by the presence of a large number of parasites in the blood and tissues. Acute infection is accompanied by an excessive activation of the immune system that includes the production of high levels of cytokines, intense activation of T and B cells, lymphadenopathy, splenomegaly, and intense inflammation associated with tissue infection niches. The acute

References

[1]  J. C. Dias, “Cecílio Roma?a, Roma?a's sign and Chagas' disease,” Revista da Sociedade Brasileira de Medicina Tropical, vol. 30, no. 5, pp. 407–413, 1997.
[2]  Z. A. Andrade, “Pathogenesis of Chagas' disease,” Research in Immunology, vol. 142, no. 2, pp. 126–129, 1991.
[3]  R. L. Tarleton, “Chagas disease: a role for autoimmunity?” Trends in Parasitology, vol. 19, no. 10, pp. 447–451, 2003.
[4]  D. Golgher and R. T. Gazzinelli, “Innate and acquired immunity in the pathogenesis of Chagas disease,” Autoimmunity, vol. 37, no. 5, pp. 399–409, 2004.
[5]  L. O. Andrade and N. W. Andrews, “Opinion: the Trypanosoma cruzi—host-cell interplay: location, invasion, retention,” Nature Reviews Microbiology, vol. 3, no. 10, pp. 819–823, 2005.
[6]  E. M. Jones, D. G. Colley, S. Tostes, E. R. Lopes, C. L. Vnencak-Jones, and T. L. McCurley, “Amplification of a Trypanosoma cruzi DNA sequence from inflammatory lesions in human chagasic cardiomyopathy,” American Journal of Tropical Medicine and Hygiene, vol. 48, no. 3, pp. 348–357, 1993.
[7]  L. A. Benvenuti, A. Roggério, H. F. G. Freitas, A. J. Mansur, A. Fiorelli, and M. L. Higuchi, “Chronic American trypanosomiasis: parasite persistence in endomyocardial biopsies is associated with high-grade myocarditis,” Annals of Tropical Medicine and Parasitology, vol. 102, no. 6, pp. 481–487, 2008.
[8]  A. R. Vago, A. M. Macedo, R. P. Oliveira et al., “Kinetoplast DNA signatures of Trypanosoma cruzi strains obtained directly from infected tissues,” The American Journal of Pathology, vol. 149, no. 6, pp. 2153–2159, 1996.
[9]  W. O. Dutra and K. J. Gollob, “Current concepts in immunoregulation and pathology of human Chagas disease,” Current Opinion in Infectious Diseases, vol. 21, no. 3, pp. 287–292, 2008.
[10]  A. Rassi Jr., A. Rassi, and J. A. Marin-Neto, “Chagas disease,” The Lancet, vol. 375, no. 9723, pp. 1388–1402, 2010.
[11]  C. Junqueira, B. Caetano, D. C. Bartholomeu et al., “The endless race between Trypanosoma cruzi and host immunity: lessons for and beyond Chagas disease,” Expert Reviews in Molecular Medicine, vol. 12, article e29, 2010.
[12]  O. Takeuchi and S. Akira, “Pattern recognition receptors and inflammation,” Cell, vol. 140, no. 6, pp. 805–820, 2010.
[13]  Z. Brener and R. T. Gazzinelli, “Immunological control of Trypanosoma cruzi infection and pathogenesis of Chagas' disease,” International Archives of Allergy and Immunology, vol. 114, no. 2, pp. 103–110, 1997.
[14]  M. A. J. Ferguson, “The structure, biosynthesis and functions of glycosylphosphatidylinositol anchors, and the contributions of trypanosome research,” Journal of Cell Science, vol. 112, no. 17, pp. 2799–2809, 1999.
[15]  M. A. J. Ferguson, M. G. Low, and G. A. M. Cross, “Glycosyl-sn-1,2-dimyristylphosphatidylinositol is covalently linked to Trypanosoma brucei variant surface glycoprotein,” The Journal of Biological Chemistry, vol. 260, no. 27, pp. 14547–14555, 1985.
[16]  I. C. Almeida, M. M. Camargo, D. O. Procópio et al., “Highly purified glycosylphosphatidylinositols from Trypanosoma cruzi are potent proinflammatory agents,” The EMBO Journal, vol. 19, no. 7, pp. 1476–1485, 2000.
[17]  I. C. Almeida and R. T. Gazzinelli, “Proinflammatory activity of glycosylphosphatidylinositol anchors derived from Trypanosoma cruzi: structural and functional analyses,” Journal of Leukocyte Biology, vol. 70, no. 4, pp. 467–477, 2001.
[18]  M. A. S. Campos, I. C. Almeida, O. Takeuchi et al., “Activation of toll-like receptor-2 by glycosylphosphatidylinositol anchors from a protozoan parasite,” The Journal of Immunology, vol. 167, no. 1, pp. 416–423, 2001.
[19]  P. S. Coelho, A. Klein, A. Talvani et al., “Glycosylphosphatidylinositol-anchored mucin-like glycoproteins isolated from Trypanosoma cruzi Trypomastigotes induce in vivo leukocyte recruitment dependent on MCP-1 production by IFN-γ-primed-macrophages,” Journal of Leukocyte Biology, vol. 71, no. 5, pp. 837–844, 2002.
[20]  F. R. S. Gutierrez, T. W. P. Mineo, W. R. Pavanelli, P. M. M. Guedes, and J. S. Silva, “The effects of nitric oxide on the immune system during Trypanosoma cruzi infection,” Memórias do Instituto Oswaldo Cruz, vol. 104, no. 1, pp. 236–245, 2009.
[21]  J. C. S. Aliberti, F. S. Machado, J. T. Souto et al., “β-chemokines enhance parasite uptake and promote nitric oxide-dependent microbiostatic activity in murine inflammatory macrophages infected with Trypanosoma cruzi,” Infection and Immunity, vol. 67, no. 9, pp. 4819–4826, 1999.
[22]  L. K. M. Shoda, K. A. Kegerreis, C. E. Suarez et al., “DNA from protozoan parasites Babesia bovis, Trypanosoma cruzi, and T. brucei is mitogenic for B lymphocytes and stimulates macrophage expression of interleukin-12, tumor necrosis factor alpha, and nitric oxide,” Infection and Immunity, vol. 69, no. 4, pp. 2162–2171, 2001.
[23]  M. A. Campos, M. Closel, E. P. Valente et al., “Impaired production of proinflammatory cytokines and host resistance to acute infection with Trypanosoma cruzi in mice lacking functional myeloid fifferentiation factor 88,” The Journal of Immunology, vol. 172, no. 3, pp. 1711–1718, 2004.
[24]  D. Martin and R. Tarleton, “Generation, specificity, and function of CD8+ T cells in Trypanosoma cruzi infection,” Immunological Reviews, vol. 201, pp. 304–317, 2004.
[25]  A. C. Oliveira, J. R. Peixoto, L. B. de Arrada et al., “Expression of functional TLR4 confers proinflammatory responsiveness to Trypanosoma cruzi glycoinositolphospholipids and higher resistance to infection with T. cruzi,” The Journal of Immunology, vol. 173, no. 9, pp. 5688–5696, 2004.
[26]  M. M. Medeiros, J. R. Peixoto, A. C. Oliveira et al., “Toll-like receptor 4 (TLR4)-dependent proinflammatory and immunomodulatory properties of the glycoinositolphospholipid (GIPL) from Trypanosoma cruzi,” Journal of Leukocyte Biology, vol. 82, no. 3, pp. 488–496, 2007.
[27]  C. Ropert and R. T. Gazzinelli, “Regulatory role of toll-like receptor 2 during infection with Trypanosoma cruzi,” Journal of Endotoxin Research, vol. 10, no. 6, pp. 425–430, 2004.
[28]  R. T. Gazzinelli and E. Y. Denkers, “Protozoan encounters with Toll-like receptor signalling pathways: implications for host parasitism,” Nature Reviews Immunology, vol. 6, no. 12, pp. 895–906, 2006.
[29]  A. Bafica, H. C. Santiago, R. Goldszmid, C. Ropert, R. T. Gazzinelli, and A. Sher, “Cutting edge: TLR9 and TLR2 signaling together account for MyD88-dependent control of parasitemia in Trypanosoma cruzi infection,” The Journal of Immunology, vol. 177, no. 6, pp. 3515–3519, 2006.
[30]  H. Hemmi, O. Takeuchi, T. Kawai et al., “A Toll-like receptor recognizes bacterial DNA,” Nature, vol. 408, no. 6813, pp. 740–745, 2000.
[31]  A. D. Chessler, L. R. Ferreira, T. H. Chang, K. A. Fitzgerald, and B. A. Burleigh, “A novel IFN regulatory factor 3-dependent pathway activated by trypanosomes triggers IFN-beta in macrophages and fibroblasts,” The Journal of Immunology, vol. 181, no. 11, pp. 7917–7924, 2008.
[32]  A. D. C. Chessler, M. Unnikrishnan, A. K. Bei, J. P. Daily, and B. A. Burleigh, “Trypanosoma cruzi triggers an early type I IFN response in vivo at the site of intradermal infection,” The Journal of Immunology, vol. 182, no. 4, pp. 2288–2296, 2009.
[33]  J. H. Kabarowski, “G2A and LPC: regulatory functions in immunity,” Prostaglandins and Other Lipid Mediators, vol. 89, no. 3-4, pp. 73–81, 2009.
[34]  L. Wang, C. G. Radu, L. V. Yang, L. A. Bentolila, M. Riedinger, and O. N. Witte, “Lysophosphatidylcholine-induced surface redistribution regulates signaling of the murine G protein-coupled receptor G2A,” Molecular Biology of the Cell, vol. 16, no. 5, pp. 2234–2247, 2005.
[35]  J. Wang, Y. Zhang, H. Wang et al., “Potential mechanisms for the enhancement of HERG K+ channel function by phospholipid metabolites,” British Journal of Pharmacology, vol. 141, no. 4, pp. 586–599, 2004.
[36]  W. Drobnik, G. Liebisch, F. X. Audebert et al., “Plasma ceramide and lysophosphatidylcholine inversely correlate with mortality in sepsis patients,” The Journal of Lipid Research, vol. 44, no. 4, pp. 754–761, 2003.
[37]  K. Kugiyama, S. A. Kerns, J. D. Morrisett, R. Roberts, and P. D. Henry, “Impairment of endothelium-dependent arterial relaxation by lysolecithin in modified low-density lipoproteins,” Nature, vol. 344, no. 6262, pp. 160–162, 1990.
[38]  D. M. Golodne, R. Q. Monteiro, A. V. Gra?a-Souza, M. A. C. Silva-Neto, and G. C. Atella, “Lysophosphatidylcholine acts as an anti-hemostatic molecule in the saliva of the blood-sucking bug Rhodnius prolixus,” The Journal of Biological Chemistry, vol. 278, no. 30, pp. 27766–27771, 2003.
[39]  R. D. Mesquita, A. B. Carneiro, A. Bafica et al., “Trypanosoma cruzi infection is enhanced by vector saliva through immunosuppressant mechanisms mediated by lysophosphatidylcholine,” Infection and Immunity, vol. 76, no. 12, pp. 5543–5552, 2008.
[40]  G. Murugesan, M. R. S. Rani, C. E. Gerber et al., “Lysophosphatidylcholine regulates human microvascular endothelial cell expression of chemokines,” Journal of Molecular and Cellular Cardiology, vol. 35, no. 11, pp. 1375–1384, 2003.
[41]  K. Lauber, S. G. Blumenthal, M. Waibel, and S. Wesselborg, “Clearance of apoptotic cells: getting rid of the corpses,” Molecular Cell, vol. 14, no. 3, pp. 277–287, 2004.
[42]  C. G. Radu, L. V. Yang, M. Riedinger, M. Au, and O. N. Witte, “T cell chemotaxis to lysophosphatidylcholine through the G2A receptor,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 1, pp. 245–250, 2004.
[43]  L. V. Yang, C. G. Radu, L. Wang, M. Riedinger, and O. N. Witte, “Gi-independent macrophage chemotaxis to lysophosphatidylcholine via the immunoregulatory GPCR G2A,” Blood, vol. 105, no. 3, pp. 1127–1134, 2005.
[44]  M. C. Connelly and F. Kierszenbaum, “Modulation of macrophage interaction with Trypanosoma cruzi by phospholipase A2-sensitive components of the parasite membrane,” Biochemical and Biophysical Research Communications, vol. 121, no. 3, pp. 931–939, 1984.
[45]  E. Y. Denkers and B. A. Butcher, “Sabotage and exploitation in macrophages parasitized by intracellular protozoans,” Trends in Parasitology, vol. 21, no. 1, pp. 35–41, 2005.
[46]  A. H. Kollien and G. A. Schaub, “The development of Trypanosoma cruzi in triatominae,” Parasitology Today, vol. 16, no. 9, pp. 381–387, 2000.
[47]  J. H. S. Kabarowski, K. Zhu, L. Q. Le, O. N. Witte, and Y. Xu, “Lysophosphatidylcholine as a ligand for the immunoregulatory receptor G2A,” Science, vol. 293, no. 5530, pp. 702–705, 2001.
[48]  K. Zhu, L. M. Baudhuin, G. Hong et al., “Sphingosylphosphorylcholine and lysophosphatidylcholine are ligands for the G protein-coupled receptor GPR4,” The Journal of Biological Chemistry, vol. 276, no. 44, pp. 41325–41335, 2001.
[49]  C. Peter, M. Waibel, C. G. Radu et al., “Migration to apoptotic “find-me” signals is mediated via the phagocyte receptor G2A,” The Journal of Biological Chemistry, vol. 283, no. 9, pp. 5296–5305, 2008.
[50]  S. K. Jackson, W. Abate, J. Parton, S. Jones, and J. L. Harwood, “Lysophospholipid metabolism facilitates Toll-like receptor 4 membrane translocation to regulate the inflammatory response,” Journal of Leukocyte Biology, vol. 84, no. 1, pp. 86–92, 2008.
[51]  K. Lauber, E. Bohn, S. M. Kr?ber et al., “Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal,” Cell, vol. 113, no. 6, pp. 717–730, 2003.
[52]  S. J. Kim, D. Gershov, X. Ma, N. Brot, and K. B. Elkon, “I-PLA2 activation during apoptosis promotes the exposure of membrane lysophosphatidylcholine leading to binding by natural immunoglobulin M antibodies and complement activation,” The Journal of Experimental Medicine, vol. 196, no. 5, pp. 655–665, 2002.
[53]  C. G. Freire-de-Lima, D. O. Nascimento, M. B. P. Soares et al., “Uptake of apoptotic cells drives the growth of a pathogenic trypanosome in macrophages,” Nature, vol. 403, no. 6766, pp. 199–203, 2000, Erratum in: Nature, vol. 404, no. 6780, pp. 904, 2000.
[54]  M. L. Belaunzarán, M. J. Wainszelbaum, E. M. Lammel et al., “Phospholipase A1 from Trypanosoma cruzi infective stages generates lipid messengers that activate host cell protein kinase c,” Parasitology, vol. 134, no. 4, pp. 491–502, 2007.
[55]  K. Oishi, R. L. Raynor, P. A. Charp, and J. F. Kuo, “Regulation of protein kinase C by lysophospholipids: potential role in signal transduction,” The Journal of Biological Chemistry, vol. 263, no. 14, pp. 6865–6871, 1988.
[56]  M. Murakami, Y. Taketomi, C. Girard, K. Yamamoto, and G. Lambeau, “Emerging roles of secreted phospholipase A2 enzymes: lessons from transgenic and knockout mice,” Biochimie, vol. 92, no. 6, pp. 561–582, 2010.
[57]  J. E. Burke and E. A. Dennis, “Phospholipase A2 structure/function, mechanism, and signaling,” The Journal of Lipid Research, vol. 50, pp. 237–242, 2009.
[58]  K. Suckling, “Phospholipase A2s: developing drug targets for atherosclerosis,” Atherosclerosis, vol. 212, no. 2, pp. 357–366, 2010.
[59]  B. B. Boyanovsky and N. R. Webb, “Biology of secretory phospholipase A2,” Cardiovascular Drugs and Therapy, vol. 23, no. 1, pp. 61–72, 2009.
[60]  D. Stanley, “The non-venom insect phospholipases A2,” Biochimica et Biophysica Acta, vol. 1761, no. 11, pp. 1383–1390, 2006.
[61]  R. L. Rana, W. Wyatt Hoback, N. A. A. Rahim, J. Bedick, and D. W. Stanley, “Pre-oral digestion: a phospholipase A2 associated with oral secretions in adult burying beetles, Nicrophorus marginatus,” Comparative Biochemistry and Physiology B, vol. 118, no. 2, pp. 375–380, 1997.
[62]  H. Tunaz and D. W. Stanley, “Phospholipase A2 in salivary glands isolated from tobacco hornworms, Manduca sexta,” Comparative Biochemistry and Physiology B, vol. 139, no. 1, pp. 27–33, 2004.
[63]  A. S. Bowman, C. L. Gengler, M. R. Surdick et al., “A novel phospholipase A2 activity in saliva of the lone star tick, Amblyomma americanum (L.),” Experimental Parasitology, vol. 87, no. 2, pp. 121–132, 1997.
[64]  K. Zhu, A. S. Bowman, J. W. Dillwith, and J. R. Sauer, “Phospholipase A2 Activity in Salivary Glands and Saliva of the Lone Star Tick (Acari: Ixodidae) during Tick Feeding,” Journal of Medical Entomology, vol. 35, no. 4, pp. 500–504, 1998.
[65]  Z. S. Derewenda and Y. S. Ho, “PAF-acetylhydrolases,” Biochimica et Biophysica Acta, vol. 1441, no. 2-3, pp. 229–236, 1999.
[66]  M. T. Cheeseman, P. A. Bates, and J. M. Crampton, “Preliminary characterisation of esterase and platelet-activating factor (PAF)-acetylhydrolase activities from cat flea (Ctenocephalides felis) salivary glands,” Insect Biochemistry and Molecular Biology, vol. 31, no. 2, pp. 157–164, 2001.
[67]  I. M. B. Francischetti, Z. Meng, B. J. Mans et al., “An insight into the salivary transcriptome and proteome of the soft tick and vector of epizootic bovine abortion, Ornithodoros coriaceus,” Journal of Proteomics, vol. 71, no. 5, pp. 493–512, 2008.
[68]  I. M. B. Francischetti, B. J. Mans, Z. Meng et al., “An insight into the sialome of the soft tick, Ornithodorus parkeri,” Insect Biochemistry and Molecular Biology, vol. 38, no. 1, pp. 1–21, 2008.
[69]  B. J. Mans, J. F. Andersen, I. M. B. Francischetti et al., “Comparative sialomics between hard and soft ticks: implications for the evolution of blood-feeding behavior,” Insect Biochemistry and Molecular Biology, vol. 38, no. 1, pp. 42–58, 2008.
[70]  I. M. B. Francischetti, V. M. Pham, B. J. Mans et al., “The transcriptome of the salivary glands of the female western black-legged tick Ixodes pacificus (Acari: Ixodidae),” Insect Biochemistry and Molecular Biology, vol. 35, no. 10, pp. 1142–1161, 2005.
[71]  E. Calvo, A. Dao, V. M. Pham, and J. M. C. Ribeiro, “An insight into the sialome of Anopheles funestus reveals an emerging pattern in anopheline salivary protein families,” Insect Biochemistry and Molecular Biology, vol. 37, no. 2, pp. 164–175, 2007.
[72]  J. Hostomská, V. Volfová, J. Mu et al., “Analysis of salivary transcripts and antigens of the sand fly Phlebotomus arabicus,” BMC Genomics, vol. 10, article 282, 2009.
[73]  J. Alves-Silva, J. M. C. Ribeiro, J. van den Abbeele et al., “An insight into the sialome of Glossina morsitans morsitans,” BMC Genomics, vol. 11, no. 1, article 213, 2010.
[74]  N. Zeidner, A. Ullmann, C. Sackal et al., “A borreliacidal factor in Amblyomma americanum saliva is associated with phospholipase A2 activity,” Experimental Parasitology, vol. 121, no. 4, pp. 370–375, 2009.
[75]  J. Vargas-Villarreal, A. Olvera-Rodríguez, B. D. Mata-Cárdenas, H. G. Martínez-Rodríguez, S. Said-Fernández, and A. Alagón-Cano, “Isolation of an Entamoeba histolytica intracellular alkaline phospholipase A2,” Parasitology Research, vol. 84, no. 4, pp. 310–314, 1998.
[76]  L. F. D. Passero, M. D. Laurenti, T. Y. Tomokane, C. E. P. Corbett, and M. H. Toyama, “The effect of phospholipase A2 from Crotalus durissus collilineatus on Leishmania (Leishmania) amazonensis infection,” Parasitology Research, vol. 102, no. 5, pp. 1025–1033, 2008.
[77]  L. E. Bertello, M. J. M. Alves, W. Colli, and R. M. de Lederkremer, “Evidence for phospholipases from Trypanosoma cruzi active on phosphatidylinositol and inositolphosphoceramide,” Biochemical Journal, vol. 345, no. 1, pp. 77–84, 2000.
[78]  R. M. Kini, “Structure-function relationships and mechanism of anticoagulant phospholipase A2 enzymes from snake venoms,” Toxicon, vol. 45, no. 8, pp. 1147–1161, 2005.
[79]  M. Rigoni, P. Caccin, S. Gschmeissner et al., “Neuroscience: equivalent effects of snake PLA2 neurotoxins and lysophospholipid-fatty acid mixtures,” Science, vol. 310, no. 5754, pp. 1678–1680, 2005.
[80]  L. Silva-Cardoso, P. Caccin, A. Magnabosco et al., “Paralytic activity of lysophosphatidylcholine from saliva of the waterbug Belostoma anurum,” Journal of Experimental Biology, vol. 213, no. 19, pp. 3305–3310, 2010.
[81]  D. W. Stanley-Samuelson, E. Jensen, K. W. Nickerson, K. Tiebel, C. L. Ogg, and R. W. Howard, “Insect immune response to bacterial infection is mediated by eicosanoids,” Proceedings of the National Academy of Sciences of the United States of America, vol. 88, no. 3, pp. 1064–1068, 1991.
[82]  D. W. Stanley-Samuelson and V. K. Pedibhotla, “What can we learn from prostaglandins and related eicosanoids in insects?” Insect Biochemistry and Molecular Biology, vol. 26, no. 3, pp. 223–234, 1996.
[83]  A. W. Ashton, S. Mukherjee, F. N. U. Nagajyothi et al., “Thromboxane A2 is a key regulator of pathogenesis during Trypanosoma cruzi infection,” The Journal of Experimental Medicine, vol. 204, no. 4, pp. 929–940, 2007.
[84]  L. A. M. Grillo, D. Majerowicz, and K. C. Gondim, “Lipid metabolism in Rhodnius prolixus (Hemiptera: reduviidae): role of a midgut triacylglycerol-lipase,” Insect Biochemistry and Molecular Biology, vol. 37, no. 6, pp. 579–588, 2007.
[85]  R. L. Wilensky, Y. Shi, E. R. Mohler et al., “Inhibition of lipoprotein-associated phospholipase A2 reduces complex coronary atherosclerotic plaque development,” Nature Medicine, vol. 14, no. 10, pp. 1059–1066, 2008.

Full-Text

comments powered by Disqus

Contact Us

service@oalib.com

QQ:3279437679

微信:OALib Journal