Alveolar MMP28 is associated with clinical outcomes and measures of lung injury in acute respiratory distress syndrome
Year: 2020
Type: article
Abstract: Background Excessive inflammation leading to increased alveolar-capillary barrier permeability remains the pathogenic model for acute respiratory distress syndrome (ARDS). Alveolar macrophage (AM) polarization has been shown to modify the activity of various matrix metalloproteinases (MMPs) that have downstream effects on key ARDS cytokines/chemokines, however the relationship between AMs, MMP28 (the newest member of the MMP family), and ARDS clinical outcomes is unknown.Methods We analyzed bronchoalveolar lavage fluid (BALF) and peripheral blood from subjects previously enrolled in a phase-II trial of omega-3 fatty acids for the treatment of ARDS ( n = 76). In a subset of these patients ( n = 25), we tested for assocations between AM- and peripheral blood monocyte (PBM)-specific MMP28 gene expression and clincal outcomes [ventilator-free days (VFDs), P a O 2 /F i O 2 ratio (P/F ratio), and sequential organ failure assessment score (SOFA)]. We tested for assocations between soluble BALF or plasma MMP28 concentrations and ARDS clinical outcomes and inflammatory mediator concentrations in the entire cohort.Results Increased AM MMP28 gene expression was significantly associated with worse VFDs and P/F ratio ( p < 0.05). Higher BALF MMP28 concentrations were associated with worse P/F, but not VFDs. Increased BALF MMP28 concentrations were associated with increased % neutrophils as well as BALF total protein, IL-6, IL-17A, and MCP-1 concentrations (all p < 0.05). Plasma MMP28 concentrations were not associated with any clinical outcome. Increased PBM MMP28 gene expression was associated with worse P/F ratio but not VFDs.Conclusions Higher AM MMP28 gene expression and BALF MMP28 concentrations are associated with poor clinical outcomes and with increased alveolar inflammatory mediators in patients with ARDS.
Source: Critical Care
Institutions: University of Washington, University of Vermont
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,290
Awards: SCCOR in Translational Research in Acute Lung Injury, Influence of TLR1 Polymorphisms on T-Regulatory Cells in ARDS, Macrophage Signaling Pathways in Acute Lung Injury and Resolution, G3787547119, MMP28 Regulation Of Macrophage Recruitment and Polarization, G5520316217, The Role of Alveolar Mononuclear Phagocytes in Acute Respiratory Distress Syndrome, G8245670873, G9000148612, Diabetes Research Center, University of Washington Interdisciplinary Center for Exposures, Diseases, Genomics & Environment
OpenAlex ID: W3015855688