The role of small heat-shock protein αB-crystalline (HspB5) in COPD pathogenesis

Abstract

Background: αB-crystallin (HspB5) is a chaperone whose role as a marker of innate immunity activation as well as its therapeutic potential have recently been investigated in several inflammatory diseases: multiple sclerosis, myocardial ischemia, and Guillain-Barré syndrome.

Aim: The aim of this study is to determine the role of αB-crystallin in chronic obstructive pulmonary disease (COPD) pathogenesis and inflammation.

Materials: Plasma levels of αB-crystallin were studied in 163 patients: 52 healthy non-COPD smokers; 20 COPD smokers in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages I-II; 43 COPD smokers in GOLD stages III-IV. Forty-eight patients were diagnosed with acute inflammatory respiratory disease. The plasma levels of αB-crystallin antibodies were determined by an enzyme-linked immunosorbent assay (Calbiochem), and were confirmed with Western blotting. Tissue expression of the protein was compared in three different groups of patients: COPD smokers, COPD nonsmokers, and in patients with age-related emphysema.

Results: The mean level of anti-αB-crystallin antibodies in non-COPD smokers was 0.291 nm. In COPD smokers it was 0.352 nm and, in patients with inflammatory lung diseases, 0.433 nm. There was a statistically significant difference between COPD smokers and healthy non-COPD smokers (P = 0.010). The same could be observed comparing the group of patients with acute inflammation and non-COPD healthy smokers (P = 0.007). There was no statistically significant difference between patients with mild/moderate inflammation and those with severe COPD. Tissue detection of the protein showed that it was significantly overexpressed in COPD smokers in comparison to COPD nonsmokers and was only slightly expressed in patients with age-related emphysema.

Conclusion: αB-crystallin is increased in patients with inflammatory lung diseases. Though unspecific, it could be used in a panel of markers discerning COPD smokers from healthy nonsmokers. As αB-crystallin is a regulator of innate immunity and a therapeutic anti-inflammatory agent, its exact role in COPD pathogenesis and therapy should be explored further.

Keywords: COPD; HspB5; chaperonopathology; pathogenesis.

Figure 1

Western blot with αB-crystalline. Notes: 2,3,5 – positive blot – COPD patients; 1,4,6,7 – negative blot – healthy smokers. Abbreviation: COPD, chronic obstructive pulmonary disease.

Figure 2

Tissue expression of αB-crystalline in lung tissues from non-COPD smokers, age-related emphysema, and COPD patients. Notes: The levels of αB-crystalline were measured in the fixed lung sections (3 mm thick) by immunohistochemical staining using rabbit polyclonal anti-αB-crystalline antibody (1:500 dilution) with the avidin-biotin-peroxidase complex method followed by hematoxylin counter staining. Brown color and the variability of its intensity represents the presence of αB-crystalline. The assessment of immunostaining intensity was performed semiquantitatively and in a blinded fashion.

Figure 3

Schematic representation of the tissue expression of αB-crystalline from COPD-smokers, non-COPD smokers, and age-related emphysema. Notes: 1 = intensive; 2 = moderate; 3 = weak. Abbreviation: COPD, chronic obstructive pulmonary disease.