Bronchoalveolar lavage fluid proteomic patterns of sulfur mustard‐exposed patients

Abstract

Sulfur mustard is an alkylating agent that reacts with ocular, respiratory, cutaneous, and bone marrow tissues. Main late respiratory complications are chronic obstructive pulmonary disease, bronchiectasis, asthma, and bronchiolitis obliterans. The aim of the present study was to identify differentially expressed proteins in bronchoalveolar lavage (BAL) fluid of control healthy and sulfur mustard-exposed lung disease patients. The BAL protein profile of ten healthy and 30 exposed patients with mild, moderate, and severe conditions (ten males in each group) were separated with 2-D SDS-PAGE and differentially expressed protein spots were successfully identified with MALDI TOF TOF MS. Among the differentially expressed proteins we observed a significant increase in vitamin D binding protein isoforms, haptoglobin isoforms, and fibrinogen especially in exposed moderate and severe lung diseases patients (p<0.01). Moreover, compared with healthy controls, significant decreases was noted in calcyphosine, surfactant protein A, and transthyretin in these patients (p<0.01). Apolipoprotein A1 was detected in all patients' BAL fluid but none of the healthy controls. Furthermore, S100 calcium-binding protein A8 was only detected in BAL fluid of moderate and severe groups. These findings will be useful to improve current methods of monitoring and helps to identify new therapeutic targets for treatment of this complicated illness.

Comparative proteome analysis of peripheral neutrophils from sulfur mustard-exposed and COPD patients

“…Expression of S100A8 and S100A12 were both significantly increased in the PMN from the SM-exposed and COPD hosts. This was in keeping with our previous study on BAL fluid from SM exposed patients that also showed significant increases in S100A8 protein (Mehrani et al, 2009). S100A12 is constitutively expressed in PMN ($5% of cytosolic protein) and, as a calcium-, zinc-, and copper-binding protein, plays a prominent role in regulation of inflammatory processes and immune responses.…”

“…Our own previous findings with SM-exposed patients revealed there were differing proteomic profiles between mild, moderate, and severe cases of exposure (Mehrani et al, 2009(Mehrani et al, , 2011. Specifically, proteomic analyses of bronchoalveolar lavage (BAL) fluids from SM-exposed patients indicated that PMN and S100A8 protein expression (mostly produced by PMN) were significantly increased in an exposure dose-related manner (Mehrani et al, 2009). Moreover, proteomic analyses of plasma from these patients revealed a significant increase in serum amyloid A1 (marker of systemic inflammation) as well (Mehrani et al, 2011).…”

“…#Spot numbers corresponding to those in Figure 1. phenomenon could also help explain why there was a significant reduction in surfactant protein A (SPA) levels in the lungs of SM-exposed patients (Mehrani et al, 2009). SPA is apparently critical to maintaining lung integrity as an increase in its degradation by NSP has been reported in several inflammatory lung diseases (Rubio et al, 2004).…”

“…The materials were then centrifuged (10,000 Â g, 10 min, 4 C); resultant supernatants were transferred to new tubes and stored at À80 C for later analyses. Protein levels in aliquots of each sample were determined using a bicinchoninic acid (BCA) assay as previously described (Mehrani et al, 2009). …”

“…In fact, through the use of proteomics, biomarkers in various diseases in which PMN play an important role have been identified (Langereis et al, 2011;Teles et al, 2012). Our own previous findings with SM-exposed patients revealed there were differing proteomic profiles between mild, moderate, and severe cases of exposure (Mehrani et al, 2009(Mehrani et al, , 2011. Specifically, proteomic analyses of bronchoalveolar lavage (BAL) fluids from SM-exposed patients indicated that PMN and S100A8 protein expression (mostly produced by PMN) were significantly increased in an exposure dose-related manner (Mehrani et al, 2009).…”