You are here: Home Published Research Calcium Restores the Macrophage Response to Non-typeable Haemophilus influenzae in COPD.

Karin A Provost, Miyuki Smith, Stephen P Arold, David L Hava, and Sanjay Sethi (2014)

Calcium Restores the Macrophage Response to Non-typeable Haemophilus influenzae in COPD.

American journal of respiratory cell and molecular biology.

Rationale: Alveolar macrophages in COPD have demonstrated impaired bacterial phagocytosis and disordered cytokine secretion, which are calcium dependent processes. We determined how calcium moderates the macrophage response to non-typeable Haemophilus influenzae (NTHI). Objective: We hypothesized that augmenting extracellular calcium during bacterial challenge would restore bacterial phagocytosis and cytokine secretion in monocyte derived macrophages from subjects with COPD. We further determined whether restoration of pattern recognition and scavenger receptors correlated with the calcium induced improvements in macrophage function. Methods: Monocytes were purified from whole blood from healthy control (n=20) and patients with moderate to severe COPD (n=35), and cultured in suspension with GM-CSF to generate monocyte-derived macrophages (MDM). The monocyte-derived macrophages were incubated with fluorescently labeled NTHI with and without calcium lactate and calcium channel inhibitors. Phagocytosis efficiency was evaluated by flow cytometry. Supernatants were assayed for cytokines using bead array technology. Cell surface receptor expression was assayed by multi-color flow cytometry. Measurements and Main Results: Extracellular calcium significantly improved phagocytosis and cytokine secretion (IL-8, TNF-α, MIP1α, MIP1β) in COPD monocyte derived macrophages. NTHI challenge led to statistically significant reductions in CD16 (FcγRIII), and extracellular calcium up regulated both CD16 and MARCO. MARCO up regulation and cytokine secretion was inhibited in the presence of specific calcium channel inhibitors. Conclusions: Extracellular calcium improved phagocytosis, restored innate cytokine secretion and increased cell surface expression of bacterial recognition receptors, CD16 and MARCO. These observations support the therapeutic use of calcium to improve macrophage function in COPD to decrease exacerbations and chronic bacterial infection.

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