German cockroach frass proteases cleave pro-matrix metalloproteinase-9

Area of Science:

• Immunology
• Biochemistry
• Allergology

Background:

• Matrix metalloproteinase (MMP)-9 is crucial in inflammation and tissue remodeling.
• Pro-MMP-9 is found in asthma patients' airways.
• Inhaled allergens often contain active proteases.

Purpose of the Study:

• To investigate if German cockroach (GC) frass and house dust mite (HDM) can cleave pro-MMP-9.
• To determine the role of serine proteases in this cleavage.
• To assess the inhibitory effect of alpha1-antitrypsin (A1AT) on GC frass-induced pro-MMP-9 activation.

Main Methods:

• Incubation of recombinant human pro-MMP-9 with GC frass and HDM.
• Treatment of GC frass with protease inhibitors (serine and cysteine).
• Assessment of pro-MMP-9 cleavage from human neutrophils.
• Incubation with A1AT and analysis of protease activity.

Main Results:

• GC frass dose- and time-dependently cleaved pro-MMP-9 via serine proteases.
• HDM showed weaker pro-MMP-9 cleavage activity.
• A1AT attenuated GC frass-induced cleavage and was itself cleaved by GC frass.
• GC frass inactivated serine protease activity in A1AT.

Conclusions:

• GC frass-derived serine proteases activate pro-MMP-9, potentially contributing to airway remodeling in asthma.
• A1AT plays a role in modulating GC frass activity in vivo.
• This study elucidates a mechanism linking aeroallergen exposure to MMP-9 activation and airway inflammation.