Source: Annual Congress 2002 - Cellular reactions in allergy in humans and animals
Disease area: Airway diseases

Abstract

The airway remodeling is a hallmark in patients with chronic asthma.Matrix metalloproteinases-2(MMP-2) has the ability to stimulate human airway smooth muscle proliferation.(Johnson S et al.Am J Phsiol 1999;277:L1109-1117).Recent evidence suggests that NO may influence MMP expression/activity,which plays a potential role in a variety of pathological conditions.We tested the hypothesis that NO-MMP pathway may contribute to airway remodeling.
The following morphometric parameters were measured by image analysis system: airway wall basement membrane perimeter(Pbm),total bronchial wall area(WAt),inner wall area(WAi) and area of smooth muscle (WAm).WAt/Pbm,WAi/Pbm and WAm/Pbm in L-arginine and asthmatic group were signifcantly higher than that in control group(p<0.01).The differences between control and L-NMMA (L-N-monomethyl arginine)group werenot significant(p>0.05).RT-PCR revealed that MMP-2 and TIMP-1 mRNA levels of lung tissue in L-arginine group[(0.82±]0.11),(0.51±]0.12)] and asthmatic group [(0.68±]0.14),(0.56±]0.10)]were significantly higher than that in control group[(0.14±]0.03),(0.11±]0.05)](p<0.01).The differences of MMP-2 mRNA between L-arginine and asthmatic group were significant(p<0.05),but not TIMP-1 mRNA (p>0.05).A significant positive correlation was found between the MMP-2 mRNA levels and nitrites/nitrates levels of lung tissue in L-arginine group and asthmatic group (r_s=0.65,0.68,p<0.05),but there was no significant correlation between nitrites/nitrates levels and TIMP-1 mRNA levels in two groups(r_s=0.23,0.18,p>0.05).L-arginine treatment increased expression of MMP-2 but not TIMP-1 mRNA in asthmatic rats,accompanying increased thickness of airway wall.L-NMMA ablated the effects of L-arginine.We postulated that nitric oxide may contribute to airway remodeling by influencing the balance between matrix metalloproteinases and tissue inhibitors of metalloproteinases.

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Citations should be made in the following way:
Y. Yuan, Z. Wang (Chengdu, China). Nitric oxide modulates expression of matrix metalloproteinase-2 in asthmatic rats: a role in airway remodeling. Eur Respir J 2002; 20: Suppl. 38, 312

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