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Bifunctional lipocalin ameliorates murine immune complex-induced acute lung injury.

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Roversi P, Ryffel B, Togbe D, Maillet I, Teixeira M, Ahmat N, Paesen GC, Lissina O, Boland W, Ploss K, Caesar JJ, Leonhartsberger S, Lea SM, Nunn MA
OpenAccess logo J Biol Chem 288 18789-802 (2013)
Related entries: 2cm4, 2cm9, 3zuo

Cited: 23 times
EuropePMC logo PMID: 23625922

Abstract

Molecules that simultaneously inhibit independent or co-dependent proinflammatory pathways may have advantages over conventional monotherapeutics. OmCI is a bifunctional protein derived from blood-feeding ticks that specifically prevents complement (C)-mediated C5 activation and also sequesters leukotriene B4 (LTB4) within an internal binding pocket. Here, we examined the effect of LTB4 binding on OmCI structure and function and investigated the relative importance of C-mediated C5 activation and LTB4 in a mouse model of immune complex-induced acute lung injury (IC-ALI). We describe two crystal structures of bacterially expressed OmCI: one binding a C16 fatty acid and the other binding LTB4 (C20). We show that the C5 and LTB4 binding activities of the molecule are independent of each other and that OmCI is a potent inhibitor of experimental IC-ALI, equally dependent on both C5 inhibition and LTB4 binding for full activity. The data highlight the importance of LTB4 in IC-ALI and activation of C5 by the complement pathway C5 convertase rather than by non-C proteases. The findings suggest that dual inhibition of C5 and LTB4 may be useful for treatment of human immune complex-dependent diseases.

Articles - 3zui mentioned but not cited (4)

  1. Bifunctional lipocalin ameliorates murine immune complex-induced acute lung injury. Roversi P, Ryffel B, Togbe D, Maillet I, Teixeira M, Ahmat N, Paesen GC, Lissina O, Boland W, Ploss K, Caesar JJ, Leonhartsberger S, Lea SM, Nunn MA. J Biol Chem 288 18789-18802 (2013)
  2. Structural Characterization and Modeling of a Respiratory Syncytial Virus Fusion Glycoprotein Nanoparticle Vaccine in Solution. Krueger S, Curtis JE, Scott DR, Grishaev A, Glenn G, Smith G, Ellingsworth L, Borisov O, Maynard EL. Mol Pharm 18 359-376 (2021)
  3. Structure and function of a family of tick-derived complement inhibitors targeting properdin. Braunger K, Ahn J, Jore MM, Johnson S, Tang TTL, Pedersen DV, Andersen GR, Lea SM. Nat Commun 13 317 (2022)
  4. Structural basis of cholesterol binding by a novel clade of dendritic cell modulators from ticks. Roversi P, Johnson S, Preston SG, Nunn MA, Paesen GC, Austyn JM, Nuttall PA, Lea SM. Sci Rep 7 16057 (2017)


Reviews citing this publication (6)

  1. Host Immune Responses to Salivary Components - A Critical Facet of Tick-Host Interactions. Ali A, Zeb I, Alouffi A, Zahid H, Almutairi MM, Ayed Alshammari F, Alrouji M, Termignoni C, Vaz IDS, Tanaka T. Front Cell Infect Microbiol 12 809052 (2022)
  2. Animal venoms/toxins and the complement system. Tambourgi DV, van den Berg CW. Mol Immunol 61 153-162 (2014)
  3. Chemical Equilibrium at the Tick-Host Feeding Interface:A Critical Examination of Biological Relevance in Hematophagous Behavior. Mans BJ. Front Physiol 10 530 (2019)
  4. Complement as a vital nexus of the pathobiological connectome for acute respiratory distress syndrome: An emerging therapeutic target. Yang Z, Nicholson SE, Cancio TS, Cancio LC, Li Y. Front Immunol 14 1100461 (2023)
  5. Immune-Mediated Retinal Vasculitis in Posterior Uveitis and Experimental Models: The Leukotriene (LT)B4-VEGF Axis. Eskandarpour M, Nunn MA, Weston-Davies W, Calder VL. Cells 10 396 (2021)
  6. Immunomodulatory Proteins in Tick Saliva From a Structural Perspective. Denisov SS, Dijkgraaf I. Front Cell Infect Microbiol 11 769574 (2021)

Articles citing this publication (13)

  1. Structural basis for therapeutic inhibition of complement C5. Jore MM, Johnson S, Sheppard D, Barber NM, Li YI, Nunn MA, Elmlund H, Lea SM. Nat Struct Mol Biol 23 378-386 (2016)
  2. Are ticks venomous animals? Cabezas-Cruz A, Valdés JJ. Front Zool 11 47 (2014)
  3. Combined inhibition of complement C5 and CD14 markedly attenuates inflammation, thrombogenicity, and hemodynamic changes in porcine sepsis. Barratt-Due A, Thorgersen EB, Egge K, Pischke S, Sokolov A, Hellerud BC, Lindstad JK, Pharo A, Bongoni AK, Rieben R, Nunn M, Scott H, Mollnes TE. J Immunol 191 819-827 (2013)
  4. Combined inhibition of complement and CD14 improved outcome in porcine polymicrobial sepsis. Skjeflo EW, Sagatun C, Dybwik K, Aam S, Urving SH, Nunn MA, Fure H, Lau C, Brekke OL, Huber-Lang M, Espevik T, Barratt-Due A, Nielsen EW, Mollnes TE. Crit Care 19 415 (2015)
  5. Complement factor 5 blockade reduces porcine myocardial infarction size and improves immediate cardiac function. Pischke SE, Gustavsen A, Orrem HL, Egge KH, Courivaud F, Fontenelle H, Despont A, Bongoni AK, Rieben R, Tønnessen TI, Nunn MA, Scott H, Skulstad H, Barratt-Due A, Mollnes TE. Basic Res Cardiol 112 20 (2017)
  6. Dual inhibition of complement factor 5 and leukotriene B4 synergistically suppresses murine pemphigoid disease. Sezin T, Murthy S, Attah C, Seutter M, Holtsche MM, Hammers CM, Schmidt E, Meshrkey F, Mousavi S, Zillikens D, Nunn MA, Sadik CD. JCI Insight 4 128239 (2019)
  7. Congress Therapeutic monoclonal antibodies for respiratory diseases: Current challenges and perspectives, March 31 - April 1, 2016, Tours, France. Desoubeaux G, Reichert JM, Sleeman M, Reckamp KL, Ryffel B, Adamczewski JP, Sweeney TD, Vanbever R, Diot P, Owen CA, Page C, Lerondel S, Le Pape A, Heuze-Vourc'h N. MAbs 8 999-1009 (2016)
  8. Evaluation of Nomacopan for Treatment of Bullous Pemphigoid: A Phase 2a Nonrandomized Controlled Trial. Sadik CD, Rashid H, Hammers CM, Diercks GFH, Weidinger A, Beissert S, Schauer F, Fettiplace J, Thaçi D, Ngai Y, Nunn MA, Zillikens D, Horváth B. JAMA Dermatol 158 641-649 (2022)
  9. The rational design of affinity-attenuated OmCI for the purification of complement C5. Macpherson A, Liu X, Dedi N, Kennedy J, Carrington B, Durrant O, Heywood S, van den Elsen J, Lawson ADG. J Biol Chem 293 14112-14121 (2018)
  10. A soft tick Ornithodoros moubata salivary protein OmCI is a potent inhibitor to prevent avian complement activation. Frye AM, Hart TM, Tufts DM, Ram S, Diuk-Wasser MA, Kraiczy P, Blom AM, Lin YP. Ticks Tick Borne Dis 11 101354 (2020)
  11. TSGP4 from Ornithodoros moubata: molecular cloning, phylogenetic analysis and vaccine efficacy of a new member of the lipocalin clade of cysteinyl leukotriene scavengers. Manzano-Román R, Díaz-Martín V, Oleaga A, Obolo-Mvoulouga P, Pérez-Sánchez R. Vet Parasitol 227 130-137 (2016)
  12. Structure and Ligand-Binding Mechanism of a Cysteinyl Leukotriene-Binding Protein from a Blood-Feeding Disease Vector. Jablonka W, Pham V, Nardone G, Gittis A, Silva-Cardoso L, Atella GC, Ribeiro JM, Andersen JF. ACS Chem Biol 11 1934-1944 (2016)
  13. Letter Allergic eye disease: Blocking LTB4/C5 in vivo suppressed disease and Th2 & Th9 cells. Eskandarpour M, Zhang X, Micera A, Zaher S, Larkin FDP, Nunn M, Bonini S, Weston-Davies W, Calder VL. Allergy 77 660-664 (2022)


Related citations provided by authors (1)

  1. The structure of OMCI, a novel lipocalin inhibitor of the complement system.. Roversi P, Lissina O, Johnson S, Ahmat N, Paesen GC, Ploss K, Boland W, Nunn MA, Lea SM J Mol Biol 369 784-93 (2007)

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