scholarly journals Linkage of neutrophil serine proteases and decreased surfactant protein-A (SP-A) levels in inflammatory lung disease

Thorax ◽  
2004 ◽  
Vol 59 (4) ◽  
pp. 318-323 ◽  
Author(s):  
F Rubio
2021 ◽  
Vol 9 (3) ◽  
pp. 212-222
Author(s):  
Peiyan Zheng ◽  
Xiaomao Zheng ◽  
Hasegawa Takehiro ◽  
Zhangkai Jason Cheng ◽  
Jingxian Wang ◽  
...  

Abstract Background and Objectives The highly variable clinical course of interstitial lung disease (ILD) makes it difficult to predict patient prognosis. Serum surfactant protein-A (SP-A) and Krebs von den Lungen-6 (KL-6) are known prognostic biomarkers. However, the clinical or pathophysiological differences in patients with these biomarkers have not been well evaluated. We investigated the clinical and pathophysiological differences through the comparison of SP-A and KL-6 levels before and after treatment. Methods This study included retrospective data from 91 patients who were treated for ILD between August 2015 and September 2019. Serum SP-A and KL-6 levels were measured before and after treatment. The patients were followed up for 3 months. Results Changes in the serum biomarkers (Delta SP-A and Delta KL-6) were found to be significantly correlated (rs = 0.523, P < 0.001); Delta SP-A and Delta KL-6 were inversely correlated with changes in pulmonary function (% predicted values of diffusing capacity for carbon monoxide [DLCO], forced vital capacity [FVC], and forced expiratory volume in 1 s [FEV1]). Patients were divided into four groups based on their Delta SP-A and Delta KL-6 levels in a cluster analysis (G1, G2, G3, and G4). Both SP-A and KL-6 were elevated in the G1 group, with all the patients enrolled classified as progressive or unchanged, and 86.4% of patients showed improved disease activity in the G4 group, where both SP-A and KL-6 levels were reduced. In the G2 group, only SP-A levels decreased post-treatment, indicating an improvement in respiratory function; the patients were not at the end stage of the disease. Only the SP-A levels increased in the G3 group with immunosuppressive treatment. Conclusions Reduced serum SP-A and/or KL-6 levels are associated with improved lung function in patients with ILD. Some patients only showed a decrease in SP-A levels could prognosis an improvement in respiratory function. When only SP-A is increased, it may imply that the patients are at an early stage of disease progression. As a result, for proper disease monitoring, measuring both markers is important.


2020 ◽  
Author(s):  
Peiyan Zheng ◽  
Xiaomao Zheng ◽  
Hasegawa Takehiro ◽  
Jingxian Wang ◽  
Mingshan Xue ◽  
...  

Abstract Background The highly variable clinical course of interstitial lung disease (ILD) makes it difficult to determine patients’ prognoses. Serum surfactant protein-A (SP-A) and Krebs von den Lungen-6 (KL-6) were known biomarkers as a monitor of the prognoses. However, the clinical or pathophysiological differences of those biomarkers are not well evaluated. Therefore, through the comparison of the changes of SP-A and KL-6 levels before and after treatment, we investigated the clinical or pathophysiological differences which are embodied by those markers. Methods This study included retrospective data for 71 patients treated for ILD at the First Affiliated Hospital of Guangzhou Medical University between August 2015 and September 2019. Serum SP-A and KL-6 levels were measured before and after treatment. The patients were followed for at least 3 months. Results Changes in the serum biomarkers (Delta SP-A and Delta KL-6) were significantly correlated (rS = 0.482, P < 0.001); Delta SP-A and Delta KL-6 were inversely correlated with changes in pulmonary function (P < 0.05). In a cluster analysis of delta SP-A and KL-6 levels, patients were classified into three groups. In the cluster analysis, in the group in which only SP-A levels decreased after treatment, 50.0% of patients recovered respiratory function and had a significant reduction of serum LDH levels.Conclusions Reduced serum SP-A and/or KL-6 levels were associated with improved lung function in patients with ILD. However, there were patients who showed only a reduction of SP-A levels after treatment. Thus, for proper disease monitoring, measuring both markers are important.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lidan Liu ◽  
Chaim Z. Aron ◽  
Cullen M. Grable ◽  
Adrian Robles ◽  
Xiangli Liu ◽  
...  

AbstractLevels of intestinal toll-like receptor 4 (TLR4) impact inflammation in the neonatal gastrointestinal tract. While surfactant protein A (SP-A) is known to regulate TLR4 in the lung, it also reduces intestinal damage, TLR4 and inflammation in an experimental model of necrotizing enterocolitis (NEC) in neonatal rats. We hypothesized that SP-A-deficient (SP-A−/−) mice have increased ileal TLR4 and inflammatory cytokine levels compared to wild type mice, impacting intestinal physiology. We found that ileal TLR4 and proinflammatory cytokine levels were significantly higher in infant SP-A−/− mice compared to wild type mice. Gavage of neonatal SP-A−/− mice with purified SP-A reduced ileal TLR4 protein levels. SP-A reduced expression of TLR4 and proinflammatory cytokines in normal human intestinal epithelial cells (FHs74int), suggesting a direct effect. However, incubation of gastrointestinal cell lines with proteasome inhibitors did not abrogate the effect of SP-A on TLR4 protein levels, suggesting that proteasomal degradation is not involved. In a mouse model of experimental NEC, SP-A−/− mice were more susceptible to intestinal stress resembling NEC, while gavage with SP-A significantly decreased ileal damage, TLR4 and proinflammatory cytokine mRNA levels. Our data suggests that SP-A has an extrapulmonary role in the intestinal health of neonatal mice by modulating TLR4 and proinflammatory cytokines mRNA expression in intestinal epithelium.


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