Biology subjects

Birukova, A.

Publications and source records attributed to Birukova, A..

3 recordsLinked to original sources

bioRxiv2026

CD163 protects against pulmonary injury and inflammation induced by acute O3 exposure

Ozone (O3)-driven pulmonary inflammation is partly regulated by damage associated molecular patterns (DAMPs) binding to scavenging receptors (SRs). However, how SRs and DAMPs regulate O3-induced pulmonary inflammation remains incompletely understood. CD163 is a SR responsible for clearing cell free hemoglobin (CFH), a DAMP which accumulates during acute pulmonary injury and is associated with worsening respiratory outcomes. We hypothesized that increased CD163 is necessary for reducing CFH levels and resolving O3-induced pulmonary injury. To test this hypothesis, we defined CD163 and CFH responses to O3 exposure in C57BL/6N (WT) and CD163 deficient (Cd163-/-) mice, as well as in human bronchoalveolar lavage fluid (BALF). In WT mice, lung Cd163 expression was significantly increased by O3 during peak inflammation and declined 24 hours post exposure. Human exposure studies revealed a diversity of Cd163 expression and a reduction of CFH following O3 exposure, suggesting regulation of this pathway in humans. When compared to WT mice, Cd163-/- mice had augmented O3-induced pulmonary injury, inflammation, and oxidative stress. Further, the antioxidant EUK-134 did not reduce O3-induced pulmonary oxidative stress in Cd163-/- mice, suggesting a role for CD163 in the pulmonary response to oxidative insults. Furthermore, compared to WT controls, Cd163-/- mice receiving an oropharyngeal aspiration of CFH had a significant increase in airspace inflammation. Combined, these findings suggest that CD163 mediated clearance of CFH is involved in resolving O3-induced pulmonary injury, inflammation, and oxidative stress. New & NoteworthyOzone (O3) is known to induce damage associated molecular patterns (DAMPs) which drive lung inflammation. The scavenging receptor, CD163, binds and clears the DAMP cell free hemoglobin (CFH), which accumulates during sterile lung injury. Our findings indicate that O3 exposure alters CD163 expression in the lung and that mice lacking Cd163 expression have more lung inflammation. Our data indicate that CD163 serves a protective role in response to acute O3 exposure perhaps through CFH clearance.

pharmacology and toxicology↗

bioRxiv2023

Tissue-resident alveolar macrophages reduce O3-induced inflammation via MerTK mediated efferocytosis

Lung inflammation, caused by acute exposure to ozone (O3) - one of the six criteria air pollutants - is a significant source of morbidity in susceptible individuals. Alveolar macrophages (AMOs) are the most abundant immune cells in the normal lung and their number increases following O3 exposure. However, the role of AMOs in promoting or limiting O3-induced lung inflammation has not been clearly defined. Here, we used a mouse model of acute O3 exposure, lineage tracing, genetic knockouts, and data from O3-exposed human volunteers to define the role and ontogeny of AMOs during acute O3 exposure. Lineage tracing experiments showed that 12, 24, and 72 h after exposure to O3 (2 ppm) for 3h all AMOs were tissue-resident origin. Similarly, in humans exposed to FA and O3 (200 ppb) for 135 minutes, we did not observe [~]21h post-exposure an increase in monocyte-derived AMOs by flow cytometry. Highlighting a role for tissue-resident AMOs, we demonstrate that depletion of tissue-resident AMOs with clodronate-loaded liposomes led to persistence of neutrophils in the alveolar space after O3 exposure, suggesting that impaired neutrophil clearance (i.e., efferocytosis) leads to prolonged lung inflammation. Moreover, depletion of tissue-resident AMO demonstrated reduced clearance of intratracheally instilled apoptotic Jurkat cells, consistent with reduced efferocytosis. Genetic ablation of MerTK - a key receptor involved in efferocytosis - also resulted in impaired clearance of apoptotic neutrophils followed O3 exposure. Overall, these findings underscore the pivotal role of tissue-resident AMOs in resolving O3-induced inflammation via MerTK-mediated efferocytosis.

immunology↗

bioRxiv2023

Allergic Asthma Responses Are Dependent on Macrophage Ontogeny

The ontogenetic composition of tissue-resident macrophages following injury, environmental exposure, or experimental depletion can be altered upon re-establishment of homeostasis. However, the impact of altered resident macrophage ontogenetic milieu on subsequent immune responses is poorly understood. Hence, we assessed the effect of macrophage ontogeny alteration following return to homeostasis on subsequent allergic airway responses to house dust mites (HDM). Using lineage tracing, we confirmed alveolar and interstitial macrophage ontogeny and their replacement by bone marrow-derived macrophages following LPS exposure. This alteration in macrophage ontogenetic milieu reduced allergic airway responses to HDM challenge. In addition, we defined a distinct population of resident-derived interstitial macrophages expressing allergic airway disease genes, located adjacent to terminal bronchi, and reduced by prior LPS exposure. These findings support that the ontogenetic milieu of pulmonary macrophages is a central factor in allergic airway responses and has implications for how prior environmental exposures impact subsequent immune responses and the development of allergy.

immunology↗