Differential effect of ARDS on alveolar macrophage efferocytosis compared to bacterial phagocytosis

Abstract

Dysregulated alveolar inflammation & neutrophil accumulation are characteristic of ARDS, however the role of alveolar macrophages (AMs) in pathogenesis is unclear. We investigated if AM efferocytic & phagocytic functions are impaired in ARDS. Methods: AMs were isolated from the bronchoalveolar lavage fluid of ventilated ICU patients with ARDS (n=5) or Sepsis (n=8, control group at risk of ARDS). AMs were used in efferocytosis & phagocytosis assays using labelled apoptotic neutrophils or pHrodo particles (E. Coli & S. Aureus) respectively. Thin layer chromatography assays determined AM conversion of cortisone to cortisol, thus measuring 11s hydroxysteroid dehydrogenase type 1 (HSD1) reductase activity in AMs. Results: ARDS AM efferocytic index was significantly impaired compared to sepsis AMs (Figure 1, medians 6.1% vs 21.0%, p=0.006). No significant difference in AM phagocytic index between ARDS & Sepsis patients was seen. ARDS AMs had significantly lower HSD1 reductase activity than sepsis AMs (medians 102 vs 853 fM/hr, p=0.02). Conclusions: Impaired AM efferocytosis in ARDS likely contributes to apoptotic neutrophil accumulation & prolonged inflammation. Cortisol stimulates efferocytosis1, therefore reduced HSD1 reductase activity in ARDS AMs may cause impaired efferocytosis. Upregulation of alveolar HSD1 activity may restore AM efferocytic function & aid ARDS resolution.