Enhanced levels of hyaluronan in lungs of patients with COPD: relationship with lung function and local inflammation.
BACKGROUND
Chronic inflammation and airway remodelling are characteristics of chronic obstructive pulmonary disease (COPD). Hyaluronan (HA) is an extracellular matrix compound with proinflammatory activity. HA levels in induced sputum from patients with COPD were measured and related to local inflammation. The expression of hyaluronan synthase 2 (HAS2) and hyaluronidase 2 (HYAL2) was analysed in lung tissue.


METHODS
Sputum was obtained from 18 patients with COPD (forced expiratory volume in 1 second (FEV(1)) 62% predicted (range 20-76)) and 14 healthy smokers. HA and inflammatory markers were measured using ELISA assays. Lung sections were obtained from five patients with severe COPD (FEV(1) <30%) and from five smokers, and mRNA levels of HAS2 and HYAL2 were analysed by polymerase chain reaction.


RESULTS
HA levels were significantly higher in the sputum from patients with COPD than controls. The COPD population appeared to consist of two subpopulations with either high or moderate HA levels. The subgroup of patients with high HA levels had lower FEV(1) than the moderate HA group. In addition, neutrophil influx and levels of interleukin-8, and the soluble tumour necrosis factor receptors R55 and R75 were significantly higher in patients with high HA levels than in those with moderate HA levels and controls. Semiquantitative analysis revealed enhanced expression of HYAL2 in lung tissue of patients with severe COPD compared with control subjects.


CONCLUSIONS
These data indicate a relationship between HA levels, local inflammation and severity of disease, and suggest enhanced breakdown of HA in the lungs of patients with COPD.
Dentener
M A
MA
Toxicology Research Institute Maastricht, Department of Respiratory Medicine, University Hospital Maastricht, P O Box 5800, 6202 AZ Maastricht, The Netherlands. Mieke.Dentener@pul.unimaas.nl
Vernooy
J H J
JH
Hendriks
S
S
Wouters
E F M
EF
D000328:Adult; D000368:Aged; D015815:Cell Adhesion Molecules / Q000378:metabolism; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D058851:GPI-Linked Proteins; D014453:Glucuronosyltransferase / Q000378:metabolism; D006801:Humans; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000378:metabolism*; D006821:Hyaluronoglucosaminidase / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000378:metabolism* / Q000503:physiopathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D012313:RNA / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013183:Sputum / Q000378:metabolism
D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D012313:RNA; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; C101754:HAS2 protein, human; D000076002:Hyaluronan Synthases; C473096:Hyal2 protein, human; D006821:Hyaluronoglucosaminidase