German cockroach frass proteases cleave pro-matrix metalloproteinase-9.
Matrix metalloproteinase (MMP)-9, secreted as pro-MMP-9, is cleaved by serine proteases at the N-terminus to generate active MMP-9. Pro-MMP-9 has been found in the bronchoalveolar lavage fluid of patients with asthma. Because many inhaled aeroallergens contain active proteases, the authors sought to determine whether German cockroach (GC) fecal remnants (frass) and house dust mite (HDM) were able to cleave pro-MMP-9. Treatment of recombinant human (rh) pro-MMP-9 with GC frass resulted in a dose- and time-dependent cleavage. This was abrogated by pretreating frass with an inhibitor of serine, but not cysteine protease activity. GC frass also induced cleavage of pro-MMP-9 from primary human neutrophils dependent on the active serine proteases in GC frass. HDM was less potent at cleaving pro-MMP-9. Alpha1-antitrypsin (A1AT), a naturally occurring protease inhibitor, attenuated GC frass-induced cleavage of pro-MMP-9. A1AT partially inactivated the serine protease activity in GC frass, while GC frass cleaved A1AT in a dose- and time-dependent manner. These data suggest that GC frass-derived serine proteases could regulate the activity of MMP-9 and that A1AT may play an important role in modulating GC frass activity in vivo. These data suggest a mechanism by which inhalation of GC frass could regulate airway remodeling through the activation of pro-MMP-9.
Hughes
Valerie S
VS
Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center and Cincinnati Children's Research Foundation, Cincinnati, Ohio 45229, USA.
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Kristen
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D000485:Allergens / Q000378:metabolism*; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000378:metabolism; D007611:Aprotinin / Q000494:pharmacology; D001249:Asthma / Q000201:enzymology / Q000276:immunology; D002478:Cells, Cultured; D003058:Cockroaches / Q000201:enzymology* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004792:Enzyme Precursors / Q000032:analysis / Q000378:metabolism*; D005243:Feces / Q000201:enzymology*; D006801:Humans; D019476:Insect Proteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology; D039981:Pyroglyphidae / Q000201:enzymology* / Q000276:immunology; D011994:Recombinant Proteins / Q000378:metabolism; D012697:Serine Endopeptidases / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000378:metabolism / Q000494:pharmacology; D013997:Time Factors; D000515:alpha 1-Antitrypsin / Q000378:metabolism / Q000494:pharmacology
D000485:Allergens; D039741:Antigens, Dermatophagoides; D004792:Enzyme Precursors; D019476:Insect Proteins; D011994:Recombinant Proteins; D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin; D007611:Aprotinin; D012697:Serine Endopeptidases; C120487:pro-matrix metalloproteinase 9; D020780:Matrix Metalloproteinase 9