title: Distinctive anti-influenza properties of recombinant collectin 43.
abstract: Collectins play important roles in innate defence against viral, fungal and bacterial pathogens. CL-43, a bovine serum collectin, which appears to have evolutionarily evolved from surfactant protein D (SP-D), shows unique structural and functional properties. In the present study, we describe the initial characterization of a recombinant CL-43 expressed in mammalian cells. Like natural CL-43, the recombinant is secreted as trimeric forms that show a preference for mannose and N-acetyl mannosamine. The natural and recombinant proteins have significantly higher haemagglutination-inhibiting activity against influenza A virus (IAV) than recombinant trimeric forms of SP-D. In contrast with the more highly multimerized forms of SP-D, namely conglutinin or mannose-binding lectin, CL-43 did not induce viral or bacterial aggregation and did not enhance IAV-induced neutrophil H(2)O(2) generation. Like SP-D, CL-43 also strongly enhanced neutrophil uptake of IAV. However, the mechanism of this enhanced internalization is different from that of SP-D in that it did not require viral aggregation. These studies establish that the trimeric structure of CL-43 is specified by its primary sequence and indicate that this naturally occurring trimeric collectin has unique antiviral activities. These findings could facilitate the development of recombinant collectins with novel antimicrobial properties.
authors.affiliation: Department of Medicine, Boston University School of Medicine, EBRC 414, 650 Albany Street, Boston, MA 02118, U.S.A. Khartsho@bu.edu
authors.forename: Kevan L
authors.initials: KL
authors.lastname: Hartshorn
authors.forename: Uffe
authors.initials: U
authors.lastname: Holmskov
authors.forename: Soren
authors.initials: S
authors.lastname: Hansen
authors.forename: Pengnian
authors.initials: P
authors.lastname: Zhang
authors.forename: Joseph
authors.initials: J
authors.lastname: Meschi
authors.forename: Tirsit
authors.initials: T
authors.lastname: Mogues
authors.forename: Mitchell R
authors.initials: MR
authors.lastname: White
authors.forename: Erika C
authors.initials: EC
authors.lastname: Crouch
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D016466:CHO Cells; D002460:Cell Line; D002850:Chromatography, Gel; D037222:Collectins; D006224:Cricetinae; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D019143:Evolution, Molecular; D006023:Glycoproteins / Q000378:metabolism; D006388:Hemagglutinins / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009980:Influenza A virus / Q000378:metabolism*; D007251:Influenza, Human / Q000517:prevention & control*; D037102:Lectins / Q000494:pharmacology*; D009005:Monosaccharides / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism; D017434:Protein Structure, Tertiary; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D012712:Serum Globulins / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D037222:Collectins; D006023:Glycoproteins; D006388:Hemagglutinins; D037102:Lectins; D009005:Monosaccharides; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants; D011994:Recombinant Proteins; D012712:Serum Globulins; C024014:conglutinin; C086954:collectin-43 protein, bovine; D006861:Hydrogen Peroxide