Elevated CXCL-8 expression in bronchoalveolar lavage correlates with disease severity in patients with acute respiratory distress syndrome resulting from tuberculosis

Hashemian, Seyed Mohamad Reza; Mortaz, Esmaeil; Tabarsi, Payam; Jamaati, Hamidreza; Maghsoomi, Zohreh; Khosravi, Adnan; Garssen, Johan; Masjedi, M R; Velayati, Ali Akbar; Folkerts, Gert; Barnes, Peter J.; Adcock, Ian M.

doi:10.1186/1476-9255-11-21

Cited by 17 publications

(12 citation statements)

References 41 publications

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“…Taken together, the global gene expression analyses show significant up regulation of inflammation, cellular immunity and tissue damage networks in the lung granulomas of active TB patients. These observations are consistent with previous reports showing elevated expression of CXCR-4, CCL-3, CXCL-8, MMP-1 and -9 (matrix metalloproteinases) in the sputum, blood, lymph node, bronchoalveolar lavage (BAL) fluid and lungs of chronic, progressive pulmonary TB patients [ 19 , 26 – 31 ]. Importantly, mRNA for the most highly expressed inflammatory proteins included MMPs, CCL3 and CXCL8, which have previously been shown to be capable of driving the maturation/cavitation of lung TB granulomas and disease progression [ 17 , 28 , 32 , 33 ].…”

Section: Resultssupporting

confidence: 93%

Lesion-Specific Immune Response in Granulomas of Patients with Pulmonary Tuberculosis: A Pilot Study

et al. 2015

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The formation and maintenance of granulomas is central to the host response to Mycobacterium tuberculosis (Mtb) infection. It is widely accepted that the lungs of patients with tuberculosis (TB) usually contain multiple infection foci, and that the granulomas evolve and differentiate independently, resulting in considerable heterogeneity. Although gene expression profiles of human blood cells have been proposed as biomarkers of Mtb infection and/or active disease, the immune profiles of discrete lesion types has not been studied extensively. Using histology, immunopathology and genome-wide transcriptome analysis, we explored the immunological profile of human lung TB granulomas. We show that although the different granulomas share core similarities in their immunological/inflammatory characteristics, they also exhibit significant divergence. Despite similar numbers of CD68+ macrophages in the different lesions, the extent of immune reactivity, as determined by the density of CD3+ T cells in the macrophage rich areas, and the extent of fibrosis, shows considerable variation. Both quantitative and qualitative differences among significantly differentially expressed genes (SDEG) were noted in each of the lesion types studied. Further, network/pathway analysis of SDEG revealed differential regulation of inflammatory response, immune cell trafficking, and cell mediated immune response in the different lesions. Our data highlight the formidable challenges facing ongoing efforts to identify peripheral blood biomarkers due to the diversity of lesion types and complexity of local immune responses in the lung.

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Section: Resultssupporting

confidence: 93%

Lesion-Specific Immune Response in Granulomas of Patients with Pulmonary Tuberculosis: A Pilot Study

et al. 2015

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“…Pro-inflammatory cytokines, IL-8 and IL-12, involved with neutrophilic response, appeared in higher levels among patients with LTD. IL-8 induces NET release in human neutrophils (59) and has been associated with autoinflammatory profile in inflammatory bowel diseases and COPD (74, 75), with autoimmune diseases mediated by neutrophils (76) and with tuberculosis pathogenesis (77, 78). We also evaluated the role of galectin-3 and metalloproteinases (MMP-1 and 8) in the LTD as they may be associated with neutrophil activation (79).…”

Section: Discussionmentioning

confidence: 99%

Imbalance of NET and Alpha-1-Antitrypsin in Tuberculosis Patients Is Related With Hyper Inflammation and Severe Lung Tissue Damage

Melo

Mesquita²,

Oliveira

et al. 2019

Front. Immunol.

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Background: Pulmonary tuberculosis (PTB) can lead to lung tissue damage (LTD) and compromise the pulmonary capacity of TB patients that evolve to severe PTB. The molecular mechanisms involved in LTD during anti-tuberculous treatment (ATT) remain poorly understood.Methods and findings: We evaluated the role of neutrophil extracellular trap (NET) and the occurrence of LTD through chest radiographic images, the microbial load in sputum, and inflammatory serum profile (IL-12p40/p70, IL-8, IL-17A, IL-23, VEGF-A, MMP-1, and -8, galectin-3, citrunillated histone H3—cit-H3, alpha-1-antitrypsin—α1AT, C-reactive protein—CRP and albumin) in a cohort of 82 PTB patients before and after 60 days of ATT. Using univariate analysis, LTD was associated with neutrophilia and increase of several inflammatory proteins involved in the neutrophil-mediated response, being cit-H3 the more related to the event. In the multivariate analysis, neutrophilia and cit-H3 appear as directly related to LTD. The analysis of the ROC curve at day 60 presented AUC of 0.97 (95.0% CI 0.95–1). Interestingly, at day 0 of ATT, these biomarkers demonstrated fine relation with LTD showing an AUC 0.92 (95.0% CI 0.86–0.99). Despite of that, the same molecules have no impact in culture conversion during ATT.Conclusions: Our data revealed that NETs may play a key role in the pathway responsible for non-specific inflammation and tissue destruction in PTB. High level of cit-H3 and low level of α1AT was observed in the serum of severe TB patients, suggesting a breakdown in the intrinsic control of NET-driven tissue damage. These data show a new insight to knowledge TB immunopathogenesis, the role of neutrophil and NET pathway. Likewise, we identified possible biomarkers to screening of PTB patients eligible to adjuvants therapies, as anti-inflammatories and alpha-1-antitrypsin.

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“…Many studies have demonstrated that CXCL5 participates in the development of lung cancer [18,19]. In addition to their function in tumor progression, the CXC-chemokines were reported to be related to the development of ARDS, including CXCL8 [20], CXCL10 [21], and CXCL1 [22]. CXCL5 and the previously studied CXC-chemokines (CXCL8, CXCL10, and CXCL1) all belong to the same family.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of Cxc Chemokine Ligand 5 (CXCL5)/Cxc Chemokine Receptor 2 (CXCR2) Bio-Axis in Mice with Acute Respiratory Distress Syndrome

et al. 2019

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Background Acute respiratory distress syndrome (ARDS) is a common acute and severe disease in clinic. Recent studies indicated that Cxc chemokine ligand 5 (CXCL5), an inflammatory chemokine, was associated with tumorigenesis. The present study investigated the role of the CXCL5/Cxc chemokine receptor 2 (CXCR2) bio-axis in ARDS, and explored the underlying molecular mechanism. Material/Methods The pathological morphology of lung tissue and degree of pulmonary edema were assessed by hematoxylin-eosin staining and pulmonary edema score, respectively. Real-time PCR and Western blot analysis were performed to detect the expression levels of CXCL5, CXCR2, Matrix metalloproteinases 2 (MMP2), and Matrix metalloproteinases 9 (MMP9) in lung tissues. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the expression levels of CXCL5 and inflammatory factors (IL-1β, IL-6, TNF-α, and IL-10) in serum. Results The results demonstrated that diffuse alveolar damage and pulmonary edema appeared in lipopolysaccharide (LPS)-induced ARDS and were positively correlated with the severity of ARDS. In addition, CXCL5 and its receptor CXCR2 were overexpressed by upregulation of MMP2 and MMP9 in lung tissues of ARDS. In addition, CXCL5 neutralizing antibody effectively alleviated inflammatory response, diffuse alveolar damage, and pulmonary edema, and decreased the expression levels of MMP2 and MMP9 compared to LPS-induced ARDS. Conclusions We found that CXCL5/CXCR2 accelerated the progression of ARDS, partly by upregulation of MMP2 and MMP9 in lung tissues with the release of inflammatory factors.

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Elevated CXCL-8 expression in bronchoalveolar lavage correlates with disease severity in patients with acute respiratory distress syndrome resulting from tuberculosis

Cited by 17 publications

References 41 publications

Lesion-Specific Immune Response in Granulomas of Patients with Pulmonary Tuberculosis: A Pilot Study

Lesion-Specific Immune Response in Granulomas of Patients with Pulmonary Tuberculosis: A Pilot Study

Imbalance of NET and Alpha-1-Antitrypsin in Tuberculosis Patients Is Related With Hyper Inflammation and Severe Lung Tissue Damage

Mechanism of Cxc Chemokine Ligand 5 (CXCL5)/Cxc Chemokine Receptor 2 (CXCR2) Bio-Axis in Mice with Acute Respiratory Distress Syndrome

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