Human mucus protease inhibitor in airway fluids is a potential defensive compound against infection with influenza A and Sendai viruses.
Tryptase Clara, a trypsin-like protease localized exclusively in and secreted from Clara cells to the bronchial epithelium of rat, proteolytically activates the infectivity of influenza A virus [H. Kido, Y. Yokogoshi, K. Sakai, M. Tashiro, Y. Kishino, A. Fukutomi, and N. Katunuma (1992) J. Biol. Chem. 267, 13573-13579]. We report here that human mucus protease inhibitor (MPI), a major inhibitor of granulocyte elastase in the lining fluids of the human respiratory tract, significantly inhibited proteolytic activation of the infectivity of influenza A and Sendai viruses by tryptase Clara in vitro and multi-cycles of mouse-adapted influenza A virus replication in rat lungs in vitro. Recombinant MPI and the C- but not the N-terminal domain of the MPI inhibited both the proteolytic activity of tryptase Clara and the activation of virus infection. The 50% inhibitory concentrations of recombinant MPI and the C-terminal domain for tryptase Clara with Sendai virus envelope glycoprotein as substrate were 7.4 and 61.6 nM, respectively. These results indicate that MPI is a defensive compound against virus infection. Since there is evidence suggesting that concentrations of MPI in respiratory fluids are insufficient for prevention of virus infection, administration of MPI in the airway may be useful for treatment of these virus infections.
Beppu
Y
Y
Division of Enzyme Chemistry, University of Tokushima.
Imamura
Y
Y
Tashiro
M
M
Towatari
T
T
Ariga
H
H
Kido
H
H
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004285:Dogs; D006801:Humans; D066298:In Vitro Techniques; D009980:Influenza A virus / Q000187:drug effects / Q000472:pathogenicity* / Q000502:physiology; D007251:Influenza, Human / Q000188:drug therapy; D008565:Membrane Proteins / Q000737:chemistry / Q000627:therapeutic use*; D051379:Mice; D018184:Paramyxoviridae Infections / Q000188:drug therapy; D010446:Peptide Fragments / Q000737:chemistry; D011487:Protein Conformation; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000737:chemistry / Q000627:therapeutic use*; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000627:therapeutic use; D018108:Respirovirus / Q000187:drug effects / Q000472:pathogenicity* / Q000502:physiology; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D053802:Tryptases; D014779:Virus Replication / Q000187:drug effects
D008565:Membrane Proteins; D010446:Peptide Fragments; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D011994:Recombinant Proteins; D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases; C075431:tryptase Clara; D053802:Tryptases