4. Conclusion
These studies demonstrate that it is possible to alter the carbohydrate recognition and viral neutralizing activities of SP-D through replacing the SP-D CRD with that of either conglutinin or MBL. These proteins have been useful tools in confirming that, 1. the enhanced ability of conglutinin to inhibit IAV infectivity as compared to SP-D results from differences in the CRDs of these proteins, and 2. the substantial greater viral aggregating and opsonizing activities of SP-D as compared to MBL result from differences in the N-terminal and collagen domains of these molecules. The chimeric collectins had significantly greater viral aggregating and neutralizing activity than either parent collectin from which they were derived. Hence, such constructs could be of therapeutic value in treatment of IAV infection. Although the two chimerae had similar activity against IAV, substantial differences were noted between their ability to bind to or aggregate bacteria (Hartshorn et al, unpublished data). Hence, there are probably significant differences between the functional properties of the CRD of conglutinin and that of MBL which need to be examined in further studies.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Anders, E.M., Hartley, C.A., and Jackson, D.C., 1990, Bovine and mouse serum B inhibitors of influenza A virus are mannose-binding lectins. Microbiology 87:4485–4489.
Anders, E.M., Hartley, C.A., Reading, P.C., and Ezekowitz, R.A.B., 1994, Complement-dependent neutralization of influenza virus by a serum mannose-binding lectin. J. Gener. Virol. 75:615–22.
Benne, C.A., Kraaijeveld, C.A., van Strijp, J.A.G., Brouwer, E., Harmsen, M., Verhoef, J., van Golde, L.M.G., and van Iwaarden, J.F., 1995, Interactions of surfactant protein A with influenza A viruses: Binding and neutralization. J. Infect. Dis. 171:335–41.
Brown-Augsburger, P., Hartshorn, K.L., Chang, D., Rust, K., Fliszar, C., Welgus, H., and Crouch, E.C., 1996, Site directed mutagenesis of Cys15 and Cys20 of pulmonary surfactant protein D: expression of a trimeric protein with altered anti-viral properties. J Biol Chem 271:13724–13730.
Crouch, E, et al 1994, Recombinant pulmonary surfactant protein D. J. Biol. Chem. 269: 15808–15813.
Eda, S., Suzuki, Y., Kase, T., Ohtani, K., Sakamoto, T., Kurimura, T., and Wakamiya, N., 1996, Recombinant bovine conglutinin, lacking N-terminal and collagenous domains, has less conglutination activity but is able to inhibit haemagglutination activity of influenza A virus. Biochem J 1996:43–48.
Eda, S, Suzuki, Y., Kawai, T., Kase, T., Ohtani, K., Fujinaga, Y., Sakamoto, T., Kurimura, T., and Wakamiya, N., 1997, Structure of a truncated human surfactant protein D is less effective in agglutinating bacteria than the native structure and fails to inhibit haemagglutination by influenza A virus. Biochem J 323:393–399.
Friis-Christiansen, P., Theil, S., Svehag, S.E., Dessau. R., Svendsen, P., Andersen, O., Laursen, J.B., and Jensenius, J.C., 1990, In vivo and in vitro antibacterial activity of conglutinin, a mammalian plasma lectin. Scand. J. Immunol. 31:453–460.
Garred, P. Madsen, H.O., Balslev, U., Hofmann, B., Pederson, C., Gerstoft, J., and Svejgaard, A., 1997, Susceptibility to HIV infection and progression of AIDS in relation to variant alleles of mannose-binding lectin. Lancet 349:236–240.
Hartley, C.A., Reading. P.C., Ward, A.C., and Anders, E.M., 1997, Changes in hemagglutinin molecule of influenza type A (H3N2) virus associated with increased virulence in mice. Arch of Virol 142:75–88.
Hartley, C.A., Jackson, D.C., and Anders, E.M. 1992, Two distinct serum mannose-binding lectins functions as B inhibitors of influenza virus: identification of bovine serum B inhibitor as conglutinin. J. Virol. 66:4358–4363.
Hartshorn, K.L., Chang, D., Rust, K., White, M.R., Heuser, J, and Crouch, E.C., 1996a, Interactions of recombinant human pulmonary surfactant protein D and SPD multimers with influenza A. Amer J Physiol 271:L753–762.
Hartshorn, K.L., Crouch, E.C., White, M.R., Colamussi, M.L., Kakkanatt, A., Tauber, B., Shepherd, V., and Sastry, K., 1998, Pulmonary surfactant proteins A and D enhance neutrophil uptake of bacteria. Amer J Physiol 274:L958–69.
Hartshorn, K.L., Crouch, E.C., White, M.R., Eggleton, P., Tauber, A.I., Chang, D., and Sastry, K.,. 1994, Evidence for a protective role of pulmonary surfactant protein D (SP-D) against influenza A viruses. J. Clin. Invest. 94:311–319.
Hartshorn, K.L., Reid, K., White, M.R., Jensenius, J.C., Moriis, S.M., Tauber, A.I., and Crouch, E.C., 1996b, Neutrophil deactivation by influenza A viruses: mechanisms of protection after viral opsonization with collectins and hemagglutination-inhibiting antibodies. Blood 87:3450–3461.
Hartshorn, K.L., Sastry, K.N., Chang, D., White, M.R., Crouch, E.C., 1999, Enhanced anti-influenza activity of a recombinant pulmonary surfactant protein D and serum conglutinin fusion protein. Amer. J. Physiol. In press.
Hartshorn, K.L., White, M.R., Shepherd, V., Reid, K., Jensenius, J.C., and Crouch, E.C., 1997, Mechanisms of anti-influenza activity of pulmonary surfactant proteins A and D: comparison with other collectins. Amer J Physiol 273:L1156–1166.
Hartshorn, K. L., Sastry, K., Brown, D., White, M.R., Okarma, T.B., Lee, Y., and Tauber, A.I., 1993a, Conglutinin acts as an opsonin for influenza A viruses. J. Immunol. 151:I–9.
Hartshorn, K.L., Sastry, K., White, M.R., Anders, E.M., Super, M., Ezekowitz, R.A.B., and Tauber, A.I., 1993b, Human mannose-binding protein functions as an opsonin for influenza A viruses. J. Clin. Invest. 91:1414–1420.
Korfhagen, T.R., 1998, Surfactant Protein D regulates surfactant phospholipid homeostasis in vivo. J Biol Chem 273:28438–28443
LeVine, AM, Bruno M., Huelsman K.M., Ross G.F., Whitsett J.A., and Korfhagen T.R., 1997, Surfactant Protein A deficient mice are susceptible to group B streptococcal infection. J. Immunol. 158:4336–4340.
Reading, PC, Allison, J., Crouch E.C., Anders E.M., 1998a, Increased susceptibility of diabetic mice to influenza virus infection: compromise of collectin-mediated host defense of the lung by glucose? J Virol 72:6884–6887.
Reading, PC, U Holmskov, and EM Anders, 1998b, Antiviral activity of bovine collectins against rotaviruses. J Gen Virol 79:22SS–2263.
Reading, P.C. Morley L.S., Crouch, E.C., and Anders E.M., 1997, Collectin-mediated antiviral host defense of the lung: evidence from influenza virus infection of mice. J Virol 71:8204–8212.
Rothmann, A.B., Mortensen, H.D., Holmskov, U., and Hojrup, P., 1997, Structural characterization of bovine collectin-43. Eur J Biochem 243:630–635.
Sastry, K.N., and Ezekowitz R.A.B., 1996, Collectins. In Collectins and innate immunity. R. Ezekowitz, K. Sastry, and K. Reid, eds. Pp. 1–7. Austin, Texas: RG Landes Co.
Schelenz, S., Malhotra, R., Sim, R.B., Holmskov, U., and Bancroft, G.J., 1995, Binding of host collectins to the pathogenic yeast Cryptococcus Neoformans: human surfactant protein D acts as an agglutinin for acapsular yeast cells. Infect and Immun 63: 3360–3366.
Turner, M.W., 1996, Functional aspects of mannose binding protein. In Collectins and innate immunity. K. Sastry and R. Ezekowitz. eds. Pp. 73–97. Austin, Texas: RG Landes.
Wakamiya, N., Okuno, Y., Sasao, F., Ueda, S., Yoshimatsu, K., Naiki, M., Kurimura, T., 1992, Isolation and characterization of Conglutinin as a influenza A virus inhibitor. Biochem. and Biophys. Res. Comm. 187: 1270–1278.
White, M.R., Crouch, E.C., Sastry, K., Guo, N., Enpelich, G., Ezekowitz, R.A.B., Hartshorn, K.L., 1999, Replacement of the collagenous domain of mannose binding lectin with that of surfactant protein D markedly alters aggregating, antiviral, and opsonic properties. In Review.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2002 Kluwer Academic Publishers
About this chapter
Cite this chapter
Hartshorn, K.L., White, M.R., Ezekowitz, R.A.B., Sastry, K., Crouch, E. (2002). Development of Chimeric Collectins with Enhanced Activity Against Influenza a Virus. In: Keisari, Y., Ofek, I. (eds) The Biology and Pathology of Innate Immunity Mechanisms. Advances in Experimental Medicine and Biology, vol 479. Springer, Boston, MA. https://doi.org/10.1007/0-306-46831-X_5
Download citation
DOI: https://doi.org/10.1007/0-306-46831-X_5
Publisher Name: Springer, Boston, MA
Print ISBN: 978-0-306-46409-6
Online ISBN: 978-0-306-46831-5
eBook Packages: Springer Book Archive