Damage-Associated Molecular Patterns and Myeloid-Derived Suppressor Cells in Bronchoalveolar Lavage Fluid in Chronic Obstructive Pulmonary Disease Patients

Abstract

Myeloid-derived suppressor cells (MDSCs) are present in the human lung microenvironment, and they may be involved in the local inflammatory process in chronic obstructive pulmonary disease (COPD). Chronic inflammation in COPD may induce immunogenic cell death of structural airway cells, causing the release of damage-associated molecular patterns (DAMPs). DAMPs may activate the innate and adaptive immune system. The relationship between MDSCs and DAMPs in COPD is poorly described in the available literature. Objectives. (1) Assessment of MDSC percentage and DAMP concentration in bronchoalveolar lavage fluid (BALF) and peripheral blood. (2) Analysis of the relationship between MDSC percentage and chosen DAMPs. Patients and Methods. 30 COPD patients were included. Using monoclonal antibodies directly conjugated with fluorochromes in flow cytometry, MDSCs were assessed in BALF and peripheral blood. The concentration of DAMPs was estimated using sandwich ELISA. Using the Bradford method, the total protein concentrations were evaluated. Results. The percentage of MDSCs among MC in BALF correlated well with the concentration of defensin and heat shock protein 27. Assessing the percentage of MDSCs among all leukocytes in BALF, we revealed a significant correlation with the concentration of defensin, hyaluronic acid, and surfactant protein A. No dependencies occurred between DAMPs and MDSCs in peripheral blood. Conclusion. MDSCs and DAMPs occur in the COPD patient lung microenvironment. Significant correlations between them found in BALF may indicate their influence on the local inflammatory process in COPD. These relationships allow better understanding of the inflammatory process in COPD.

Human lung cDC1 drive increased perforin-mediated NK cytotoxicity in chronic obstructive pulmonary disease

“…Interestingly, in response to DC-secreted IL-18, NKs themselves release HMGB1, which permits immature DCs to escape NK-mediated lysis ( 47 ). Other DAMPS, including β-defensins and HSPs, are also increased in COPD and have a known role in DC recruitment and/or activation ( 20 ). Because airway cDC1 are relatively short-lived cells that must be replenished continuously from the bone marrow, defining the interactions that drive activation represents a crucial knowledge gap.…”

“…Viable lung DCs and autologous peripheral blood NKs were resuspended in culture media ( 20 ). Pan-DCs and blood NKs were pretreated with LPS (1 µg/mL) or media for 6 h before mixing at a 1:1 ratio.…”

Regulatory T cells, damage-associated molecular patterns, and myeloid-derived suppressor cells in bronchoalveolar lavage fluid interlinked with chronic obstructive pulmonary disease severity

“…Tregs were assessed according to the immunophenotype: CD3 + /CD4 + /CD25 high /FoxP3 + , [30] while MDSCs were defined as cells with SSC low /Lin-1 neg /HLA-DR neg/low /CD11 + /CD33 + /CD45 + [12,31] . Cytometric analysis was performed using appropriate isotype controls.…”

Регуляторные Механизмы Системного Воспаления При Респираторной Патологии

“…Помимо использования в качестве антигенов для естественных антител, Ox-PLs могут функционировать в качестве лигандов для рецепторов мусорщика (scavenger receptors) и С-реактивного белка [312]. Ox-PLs стимулируют несколько типов рецепторов, расположенных на поверхности клетки или в ядре, в том числе сопряженные с G-белками рецепторы (G protein-coupled receptor 120 (GPR120)), рецепторы тирозинкиназы, рецепторы PPARs (рецепторы, активированные пролифератором пероксисом (Peroxisome proliferator activated receptor (PPARγ и PPARα) и TLRs [165].…”

“…В обзоре Nasim Dana и соавт. проанализированы взаимоотношения между PPARs и TLRs [165]. Интересно, что существует достаточно доказательств, демонстрирующих двусторонние взаимосвязи между TLRs и PPARs.…”