title: SALO, a novel classical pathway complement inhibitor from saliva of the sand fly Lutzomyia longipalpis.
abstract: Blood-feeding insects inject potent salivary components including complement inhibitors into their host's skin to acquire a blood meal. Sand fly saliva was shown to inhibit the classical pathway of complement; however, the molecular identity of the inhibitor remains unknown. Here, we identified SALO as the classical pathway complement inhibitor. SALO, an 11 kDa protein, has no homology to proteins of any other organism apart from New World sand flies. rSALO anti-complement activity has the same chromatographic properties as the Lu. longipalpis salivary gland homogenate (SGH)counterparts and anti-rSALO antibodies blocked the classical pathway complement activity of rSALO and SGH. Both rSALO and SGH inhibited C4b deposition and cleavage of C4. rSALO, however, did not inhibit the protease activity of C1s nor the enzymatic activity of factor Xa, uPA, thrombin, kallikrein, trypsin and plasmin. Importantly, rSALO did not inhibit the alternative or the lectin pathway of complement. In conclusion our data shows that SALO is a specific classical pathway complement inhibitor present in the saliva of Lu. longipalpis. Importantly, due to its small size and specificity, SALO may offer a therapeutic alternative for complement classical pathway-mediated pathogenic effects in human diseases.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Belo Horizonte, MG, Brasil.
authors.forename: Viviana P
authors.initials: VP
authors.lastname: Ferreira
authors.affiliation: Laboratório de Fisiologia de Insetos Hematófagos, Departamento de Parasitologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Fazito Vale
authors.affiliation: The University of Texas Health Science Center at Tyler, Tyler, TX.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Pangburn
authors.affiliation: Vector Molecular Biology Section, LMVR, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD.
authors.forename: Maha
authors.initials: M
authors.lastname: Abdeladhim
authors.affiliation: Laboratório de Fisiologia de Insetos Hematófagos, Departamento de Parasitologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.|Vector Molecular Biology Section, LMVR, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD.
authors.forename: Antonio Ferreira
authors.initials: AF
authors.lastname: Mendes-Sousa
authors.affiliation: Vector Molecular Biology Section, LMVR, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD.
authors.forename: Iliano V
authors.initials: IV
authors.lastname: Coutinho-Abreu
authors.affiliation: Vector Molecular Biology Section, LMVR, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD.
authors.forename: Manoochehr
authors.initials: M
authors.lastname: Rasouli
authors.affiliation: Vector Molecular Biology Section, LMVR, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Brandt
authors.affiliation: Vector Molecular Biology Section, LMVR, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD.
authors.forename: Claudio
authors.initials: C
authors.lastname: Meneses
authors.affiliation: Laboratório de Fisiologia de Insetos Hematófagos, Departamento de Parasitologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.
authors.forename: Kolyvan Ferreira
authors.initials: KF
authors.lastname: Lima
authors.affiliation: Laboratório de Fisiologia de Insetos Hematófagos, Departamento de Parasitologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Nascimento Araújo
authors.affiliation: Laboratório de Fisiologia de Insetos Hematófagos, Departamento de Parasitologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.
authors.forename: Marcos Horácio
authors.initials: MH
authors.lastname: Pereira
authors.affiliation: Biology Center of the Czech Academy of Sciences, Budweis,CZ-370 05, Czech Republic.
authors.forename: Michalis
authors.initials: M
authors.lastname: Kotsyfakis
authors.affiliation: Vector Molecular Biology Section, LMVR, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD.
authors.forename: Fabiano
authors.initials: F
authors.lastname: Oliveira
authors.affiliation: Vector Molecular Biology Section, LMVR, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD.
authors.forename: Shaden
authors.initials: S
authors.lastname: Kamhawi
authors.affiliation: Vector Biology Section, LMVR, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD.
authors.forename: Jose M C
authors.initials: JM
authors.lastname: Ribeiro
authors.affiliation: Laboratório de Fisiologia de Insetos Hematófagos, Departamento de Parasitologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.
authors.forename: Nelder F
authors.initials: NF
authors.lastname: Gontijo
authors.affiliation: Vector Molecular Biology Section, LMVR, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD.|Vaccine Formulation Laboratory, Department of Biochemistry, University of Lausanne, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Collin
authors.affiliation: Vector Molecular Biology Section, LMVR, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD.
authors.forename: Jesus G
authors.initials: JG
authors.lastname: Valenzuela
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003167:Complement Activation / Q000187:drug effects; D003172:Complement C1 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D003181:Complement C4 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D051056:Complement Inactivating Agents / Q000494:pharmacology*; D003171:Complement Pathway, Classical / Q000187:drug effects*; D006801:Humans; D019476:Insect Proteins / Q000494:pharmacology*; D011576:Psychodidae / Q000276:immunology* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D012463:Saliva / Q000378:metabolism*
chemical_list: D003172:Complement C1; D003181:Complement C4; D051056:Complement Inactivating Agents; D019476:Insect Proteins; D011994:Recombinant Proteins