title: Escherichia coli Braun Lipoprotein (BLP) exhibits endotoxemia - like pathology in Swiss albino mice.
abstract: The endotoxin lipopolysaccharide (LPS) promotes sepsis, but bacterial peptides also promote inflammation leading to sepsis. We found, intraperitoneal administration of live or heat inactivated E. coli JE5505 lacking the abundant outer membrane protein, Braun lipoprotein (BLP), was less toxic than E. coli DH5α possessing BLP in Swiss albino mice. Injection of BLP free of LPS purified from E. coli DH5α induced massive infiltration of leukocytes in lungs and liver. BLP activated human polymorphonuclear cells (PMNs) ex vivo to adhere to denatured collagen in serum and polymyxin B independent fashion, a property distinct from LPS. Both LPS and BLP stimulated the synthesis of platelet activating factor (PAF), a potent lipid mediator, in human PMNs. In mouse macrophage cell line, RAW264.7, while both BLP and LPS similarly upregulated TNF-α and IL-1β mRNA; BLP was more potent in inducing cyclooxygenase-2 (COX-2) mRNA and protein expression. Peritoneal macrophages from TLR2-/-mice significantly reduced the production of TNF-α in response to BLP in contrast to macrophages from wild type mice. We conclude, BLP acting through TLR2, is a potent inducer of inflammation with a response profile both common and distinct from LPS. Hence, BLP mediated pathway may also be considered as an effective target against sepsis.
authors.affiliation: Department of Studies in Biochemistry, University of Mysore, Manasagangothri, Mysore - 570 006, Karnataka, India.
authors.forename: Chikkamenahalli Lakshminarayana
authors.initials: CL
authors.lastname: Lakshmikanth
authors.affiliation: Department of Studies in Biochemistry, University of Mysore, Manasagangothri, Mysore - 570 006, Karnataka, India.
authors.forename: Shancy Petsel
authors.initials: SP
authors.lastname: Jacob
authors.affiliation: Department of Veterinary and Biomedical Sciences, Center for Molecular Immunology and Infectious Disease and Center for Molecular Toxicology and Carcinogenesis, 115 Henning Building, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Avinash Kundadka
authors.initials: AK
authors.lastname: Kudva
authors.affiliation: Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
authors.forename: Calivarathan
authors.initials: C
authors.lastname: Latchoumycandane
authors.affiliation: Department of Protein Chemistry &Technology, Central Food Technological Research Institute/CSIR, Mysore - 570 020, Karnataka, India.
authors.forename: Puttaraju Srikanta Murthy
authors.initials: PS
authors.lastname: Yashaswini
authors.affiliation: Department of Studies in Biochemistry, University of Mysore, Manasagangothri, Mysore - 570 006, Karnataka, India.
authors.forename: Mosale Seetharam
authors.initials: MS
authors.lastname: Sumanth
authors.affiliation: Laboratótio de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, 21045-900, Brazil.
authors.forename: Cassiano F
authors.initials: CF
authors.lastname: Goncalves-de-Albuquerque
authors.affiliation: Laboratótio de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, 21045-900, Brazil.
authors.forename: Adriana R
authors.initials: AR
authors.lastname: Silva
authors.affiliation: Department of Protein Chemistry &Technology, Central Food Technological Research Institute/CSIR, Mysore - 570 020, Karnataka, India.
authors.forename: Sridevi Annapurna
authors.initials: SA
authors.lastname: Singh
authors.affiliation: Laboratótio de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, 21045-900, Brazil.
authors.forename: Hugo C
authors.initials: HC
authors.lastname: Castro-Faria-Neto
authors.affiliation: Department of Veterinary and Biomedical Sciences, Center for Molecular Immunology and Infectious Disease and Center for Molecular Toxicology and Carcinogenesis, 115 Henning Building, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Sandeep Kumble
authors.initials: SK
authors.lastname: Prabhu
authors.affiliation: Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: McIntyre
authors.affiliation: Department of Studies in Biochemistry, University of Mysore, Manasagangothri, Mysore - 570 006, Karnataka, India.
authors.forename: Gopal Kedihithlu
authors.initials: GK
authors.lastname: Marathe
mesh_terms: D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000633:toxicity*; D002448:Cell Adhesion / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000276:immunology; D019446:Endotoxemia / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D029968:Escherichia coli Proteins / Q000633:toxicity*; D005786:Gene Expression Regulation; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008074:Lipoproteins / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D009195:Peroxidase / Q000235:genetics / Q000276:immunology; D010972:Platelet Activating Factor / Q000235:genetics / Q000276:immunology; D061251:Primary Cell Culture; D000067996:RAW 264.7 Cells; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: D001425:Bacterial Outer Membrane Proteins; D029968:Escherichia coli Proteins; C508585:IL1B protein, human; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D008074:Lipoproteins; D010972:Platelet Activating Factor; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human