Abstract
There is little information on mucins versus potential regulatory factors in the peripheral airway lumen of long-term smokers with (LTS+) and without (LTS-) chronic obstructive pulmonary disease (COPD). We explored these matters in bronchoalveolar lavage (BAL) samples from two study materials, both including LTS+ and LTS- with a very similar historic exposure to tobacco smoke, and healthy non-smokers (HNSs; n=4-20/group). Utilizing slot blot and immunodetection of processed (filtered and centrifuged), as well as unprocessed BAL samples from one of the materials, we compared the quantity and fraction of large complexes of mucins. All LTS displayed an enhanced (median) level of MUC5AC compared with HNS. LTS- displayed a higher level of large MUC5AC complexes than HNS while LTS+ displayed a similar trend. In all LTS, total MUC5AC correlated with blood leukocytes, BAL neutrophil elastase and net gelatinase activity. Large mucin complexes accounted for most MUC5B, without clear group differences. In all LTS, total MUC5B correlated with total MUC5AC and local bacteria. In the same groups, large MUC5B complexes correlated with serum cotinine. MUC1 was increased and correlated with BAL leukocytes in all LTS whereas MUC2 was very low and without clear group differences. Thus, the main part of MUC5AC and MUC5B is present as large complexes in the peripheral airway lumen and historic as well as current exposure to tobacco smoke emerge as potential regulatory factors, regardless of COPD per se. Bacteria, leukocytes and proteinases also constitute potential regulatory factors, of interest for future therapeutic strategies.
Highlights
Chronic obstructive pulmonary disease (COPD) is defined as a chronic airway disorder caused by inhalation of noxious particles or gases, including tobacco smoke; a disorder that is characterized by persistent respiratory symptoms and airflow limitation, as well as variable inflammatory patterns and tissue remodeling throughout the airways [1,2,3,4]
For Material 2 only, we monitored chronic bronchitis but only two subjects had chronic bronchitis. One such subject was included in the long-term smoker (LTS)− group and one in the LTS+ group
Since a 2.5-fold increase in the level of MUC5AC in sputum has previously been observed in long-term smokers (LTSs) [18], we found the corresponding difference that we detected in bronchoalveolar lavage (BAL) samples smaller than expected
Summary
Chronic obstructive pulmonary disease (COPD) is defined as a chronic airway disorder caused by inhalation of noxious particles or gases, including tobacco smoke; a disorder that is characterized by persistent respiratory symptoms and airflow limitation, as well as variable inflammatory patterns and tissue remodeling throughout the airways [1,2,3,4]. COPD is largely a preventable disease, since long-term tobacco smoking remains the most common known cause [1]. There is an unmet medical need for more efficacious and tolerable therapy to improve the long-term prognosis of COPD. To develop such therapy, the understanding of pathogenic target mechanisms must be improved
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