Phenotypic characterization of alveolar monocyte recruitment in acute respiratory distress syndrome

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.

Lung-Specific Overexpression of CC Chemokine Ligand (CCL) 2 Enhances the Host Defense to Streptococcus pneumoniae Infection in Mice: Role of the CCL2-CCR2 Axis

“…Recent observations from our group demonstrated that highly elevated CCL2 levels in BAL fluids of critically ill patients with septic ARDS were associated with the severity of respiratory failure (15). Because septic ARDS patients are at considerably increased risk of developing fibrotic responses in the late phase of the disease, it will be important to evaluate whether CCL2-triggered mechanisms outlined in the current study may also apply to patients with septic ARDS, where increased CCL2 levels and sustained inflammatory activation coincide within the same lung compartment.…”

“…Fibroproliferative responses are clinical complications frequently developing in the late phase of acute lung injury, as observed in severe pneumonia leading to acute respiratory distress syndrome (ARDS) (13)(14)(15). Examination of lung tissue sections from S. pneumoniae-infected mice of the two treatment groups revealed that 75% of the CCL2 overexpressing mice as compared with 25% of the wild-type mice developed bronchiolitis obliterans with organizing pneumonia by day 7 postinfection (Fig.…”

Monocytes Control Second-Phase Neutrophil Emigration in Established Lipopolysaccharide-induced Murine Lung Injury

“…PBMs are increasingly being recognized in many organ systems as orchestrators of leukocyte recruitment (11,22), prime initiators of endothelial damage (44,45), and pivotal contributors to fibrogenesis (32,46). However, despite the significant body of work suggesting that monocytes contribute to ALI (11,13,16,39,44,45,(47)(48)(49), no published reports exist of therapeutic monocyte depletion in established experimental ALI. We hypothesized in this study that infiltrating PBMs play a major role in regulating ongoing neutrophil recruitment and consequent vascular leak and that depletion of the PBM pool is a therapeutic target in the setting of established ALI.…”

“…These descriptions, alongside the recent discovery of patrolling sentinel monocytes within the vasculature (6), highlight PBMs' potential role in sensing and directing the inflammatory response. The importance of PBMs in acute inflammation offers a potential therapeutic window because they mobilize from the bone marrow and circulate in the peripheral vasculature before tissue infiltration in ALI (14)(15)(16). Hence, targeting PBMs and the mechanisms by which they could influence neutrophil emigration may provide a valuable interventional strategy.…”

Mesenchymal Stromal Cells Modulate Macrophages in Clinically Relevant Lung Injury Models by Extracellular Vesicle Mitochondrial Transfer

“…Macrophages are polarized by environmental cues and adopt different phenotypes. M1 proinflammatory and M2 antiinflammatory phenotypes are associated with the acute and resolving phases, respectively, of inflammation in ARDS (4,5). Mesenchymal stromal cells (MSCs) are increasingly recognized as a promising candidate therapy for ARDS (6).…”