Eosinophil induced airway smooth muscle remodelling in asthma
Journal Title: Pulmonologija ir alergologija - Year 2017, Vol 1, Issue 1
Abstract
Characteristics of the studied subjects: A total of 39 nonsmoking adults participated in the study (22 steroid-free patients with intermittent or mild-to moderate persistent asthma, and 17 healthy participants who constituted the control group). All asthma patients had significantly higher numbers of peripheral blood eosinophils, and increased eosinophil number in induced sputum. All patients recieved bronchial allergen challenge with D. pteronyssinus at different concentrations (0.1, 1.0, 10.0, and 33.3 IR/mL). The results of the test were considered positive if there was a fall in FEV1 of 20 % or more from the baseline value. Eosinophil integrin expression: We observed that asthmatic eosinophils had 3.7 ± 1.0-fold of α4, 4.6 ± 1.4-fold of αM, 4.1±1.1-fold of β1 and 16.8 ± 4.9-fold of β2 more mRNA, compared to eosinophils from healthy individuals. We also determined the effects of eosinophil adhesion to cultured human ASM cells on the abundance of α4, αM, β1 and β2 mRNA. We collected adherent asthmatic and healthy eosinophils after 24 h of co-culture with ASM cells, and determined that asthmatic eosinophils exhibited a 6.0 ± 1.8-fold increase in α4 mRNA compared to eosinophil that were not incubated with ASM cells (p<0.05). In striking contrast, eosinophils from healthy donors exhibited no change in α4, β1 and β2 mRNA after 24 co-culture with human ASM cells. We measured no change in other integrins subunits mRNA abundance after co-culture with ASM cells in eosinophils from either healthy or asthmatic donors. Adhesion of eosinophils: Adhesion of eosinophils from asthma patients was significantly greater than adhesion of eosinophils from healthy subjects at time points from 30 to 240 min. Moreover, the adhesion of eosinophils to ASM cells did not differ among time points within the asthma patients group or within the healthy subjects group. Integrin-blocking peptide RGDS had a significant effect on reducing eosinophil adhesion in both the control and asthma groups, with similar percentage values. In the control group, adhesion decreased by an average of 9.54 ± 0.71%, while blocking of eosinophil integrin in the asthma group reduced adhesion by an average of 13.53 ± 2.70%. Moreover, the bronchial challenge had an effect increasing adhesion of asthmatic eosinophils. TGF-β1 production: We found that the gene was expressed to a greater extent in the asthmatic eosinophils group compared with the healthy eosinophils group and bronchial challenge increased that differences even more. Eosinophils from both groups were observed to induce TGF-β1 gene expression in ASM cels asthma group gene overexpression. Blocking of eosinophils imtegrins reduced the influence of eosinophils from the both eosinophils groups. Gene expression levels were confirmed and reflected to protein levels in co-cutures growth medium. Eosinophils stimulated WNT-5a and ECM protein production: After 24 h of co-culture with eosinophils from asthmatic subjects, Wnt- 5a gene expression in ASM cells increased 4.80 ± 1.34 fold, collagen gene expression increased 2.13 ± 0.23 fold compared with control ASM cells cultured without eosinophils. No significant effect on these genes expression was detected after incubation of ASMC with eosinophils from healthy subjects. Moreover, eosinophils from both asthmatic and healthy subjects significantly increased fibronectin gene expression in ASM cells compared with control ASM cells cultured without eosinophils (1.71 ± 0.25 fold and 1.73 ± 0.20 fold). Reducing the ability of eosinophils to adhere to the surface of ASM cells or ECM protein by integrin-blocking using the RGDS peptide had a significant inhibitory effect on WNT-5a, fibronectin and collagen genes expression. Eosinophil-induced ASM cell proliferation Eosinophils from asthma patients significantly increased ASM cells up tp 21% while healthy eosinophils only by 5 %. After ASM cells were incubated with eosinophils from the asthma group and integrins were blocked, ASM cell proliferation reduced by 10.5%, while eosinophil integrin-blocking in the control group showed that the proliferative effect was reduced to 2.15%.
Authors and Affiliations
Andrius Januškevičius, Ieva Janulaitytė, Virginija Kalinauskaitė-Žukauskė, Kęstutis Malakauskas
Keywords
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