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Phenotypic characterization of alveolar monocyte recruitment in acute respiratory distress syndrome
1Department of Internal Medicine, Justus-Liebig-University, 35385 Giessen, Germany. simone.rosseau@charite.de
Abstract:
In 49 acute respiratory distress syndrome (ARDS) patients, the phenotype of alveolar macrophages (AMs) was analyzed by flow cytometry. Bronchoalveolar lavage (BAL) was performed within 24 h after intubation and on days 3-5, 9-12, and 18-21 of mechanical ventilation. The 27E10(high)/CD11b(high)/CD71(low)/ 25F9(low)/HLA DR(low)/RM3/1(low) AM population in the first BAL indicated extensive monocyte influx into the alveolar compartment. There was no evidence of increased local AM proliferation as assessed by nuclear Ki67 staining. Sequential BAL revealed two distinct patient groups. In one, a decrease in 27E10 and CD11b and an increase in CD71, 25F9, HLA DR, and RM3/1 suggested a reduction in monocyte influx and maturation of recruited cells into AMs, whereas the second group displayed sustained monocyte recruitment. In the first BAL from all patients, monocyte chemoattractant protein (MCP)-1 was increased, and AMs displayed elevated MCP-1 gene expression. In sequential BALs, a decrease in MCP-1 coincided with the disappearance of monocyte-like AMs, whereas persistent upregulation of MCP-1 paralleled ongoing monocyte influx. A highly significant correlation between BAL fluid MCP-1 concentration, the predominance of monocyte-like AMs, and the severity of respiratory failure was noted.
Insights
In acute respiratory distress syndrome (ARDS), alveolar macrophages (AMs) phenotypes reveal distinct patient groups based on monocyte influx. Monocyte chemoattractant protein-1 (MCP-1) levels correlate with monocyte-like AMs and respiratory failure severity.
Area of Science:
- Immunology
- Pulmonology
- Critical Care Medicine
Background:
- Alveolar macrophages (AMs) play a critical role in lung immunity and inflammation.
- Understanding AM phenotypes in acute respiratory distress syndrome (ARDS) is crucial for developing targeted therapies.
Purpose of the Study:
- To analyze alveolar macrophage (AM) phenotypes in patients with acute respiratory distress syndrome (ARDS) using flow cytometry.
- To investigate the relationship between AM phenotype, monocyte chemoattractant protein-1 (MCP-1) levels, and ARDS severity.
Main Methods:
- Collected bronchoalveolar lavage (BAL) fluid from 49 ARDS patients at multiple time points during mechanical ventilation.
- Utilized flow cytometry to analyze AM phenotypes, including expression of markers like 27E10, CD11b, CD71, 25F9, HLA-DR, and RM3/1.
- Assessed AM proliferation using Ki67 staining and measured MCP-1 levels in BAL fluid and AMs.
Main Results:
- Identified distinct AM phenotypes in ARDS patients, characterized by either a decrease in monocyte-like AMs (suggesting maturation) or sustained monocyte recruitment.
- Found elevated MCP-1 levels and gene expression in AMs, correlating with monocyte influx.
- Demonstrated a significant correlation between high BAL fluid MCP-1 concentration, the presence of monocyte-like AMs, and increased respiratory failure severity.
Conclusions:
- ARDS patients exhibit heterogeneous AM responses, with distinct patterns of monocyte recruitment and maturation.
- MCP-1 is a key mediator of monocyte recruitment into the alveolar space in ARDS.
- MCP-1 levels and monocyte-like AM predominance serve as potential biomarkers for ARDS severity.
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