Airway proteoglycans are differentially altered in fatal asthma.
It has been suggested that airway remodelling is responsible for the persistent airway obstruction and decline in lung function observed in some asthmatic patients. The small airways are thought to contribute significantly to this functional impairment. Proteoglycans (PGs) are important components of the extracellular matrix (ECM) in the lungs. Besides controlling biophysical properties of the ECM, they play important roles in the regulation of some cytokines. Increased subepithelial PG deposition in the airways of mild asthmatics has been reported. However, there are no data on the PG content in small airways in asthma. This study has compared the content and distribution of PGs in large and small airways of patients who died of asthma with those in control lungs. Immunohistochemistry and image analysis were used to determine the content of lumican, decorin, biglycan, and versican in large (internal perimeter >6 mm) and small (internal perimeter < or =6 mm) airways of 18 patients who had died of asthma (A) and ten controls (C). The results were expressed as PG area (microm2)/epithelial basement membrane length (microm). The main differences between asthmatics and controls were observed in the small airways. There was a significant decrease in decorin and lumican contents in the external area of small airways in asthmatics (decorin: A = 1.05 +/- 0.27 microm, C = 3.97 +/- 1.17 microm, p = 0.042; lumican: A = 1.97 +/- 0.37 microm, C = 5.66 +/- 0.99 microm, p = 0.002). A significant increase in versican content in the internal area of small and large airways in asthmatics was also observed (small: A = 7.48 +/- 0.84 microm, C = 5.16 +/- 0.61 microm, p = 0.045; large: A = 18.38 +/- 1.94 microm, C = 11.90 +/- 2.86 microm, p = 0.028). The results show that PGs are differentially expressed in the airways of fatal asthma and may contribute to airway remodelling. These data reinforce the importance of the small airways in airway remodelling in asthma.
de Medeiros Matsushita
Marcus
M
Department of Pathology, School of Medicine, University of Sao Paulo, Brazil.
da Silva
Luiz Fernando Ferraz
LF
dos Santos
Mario Adriano
MA
Fernezlian
Sandra
S
Schrumpf
Jasmijn A
JA
Roughley
Peter
P
Hiemstra
Pieter S
PS
Saldiva
Paulo Hilário Nascimento
PH
Mauad
Thais
T
Dolhnikoff
Marisa
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D001344:Autopsy; D011508:Chondroitin Sulfate Proteoglycans / Q000032:analysis; D058575:Decorin; D016326:Extracellular Matrix Proteins; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007632:Keratan Sulfate / Q000032:analysis; D037181:Lectins, C-Type; D000071234:Lumican; D008168:Lung / Q000737:chemistry* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011509:Proteoglycans / Q000032:analysis*; D013224:Status Asthmaticus / Q000378:metabolism* / Q000473:pathology; D053675:Versicans
D011508:Chondroitin Sulfate Proteoglycans; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; C000604306:LUM protein, human; D037181:Lectins, C-Type; D000071234:Lumican; D011509:Proteoglycans; C508322:VCAN protein, human; D053675:Versicans; D007632:Keratan Sulfate