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CD163 is expressed and modulated in human pulmonary artery smooth muscle cells: Implications for pulmonary artery hypertension

Latha Ramakrishnan, Sharon Mumby, John S. Wort, Gregory J. Quinlan
European Respiratory Journal 2015 46: PA4901; DOI: 10.1183/13993003.congress-2015.PA4901
Latha Ramakrishnan
Vascular Biology Group, National Heart and Lung Institute, Imperial College London, London, United Kingdom
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Sharon Mumby
Vascular Biology Group, National Heart and Lung Institute, Imperial College London, London, United Kingdom
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John S. Wort
Vascular Biology Group, National Heart and Lung Institute, Imperial College London, London, United Kingdom
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Gregory J. Quinlan
Vascular Biology Group, National Heart and Lung Institute, Imperial College London, London, United Kingdom
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Abstract

Pulmonary Arterial Hypertension (PAH) is a rare but fatal disease characterised by remodelling of the pulmonary vasculature, increased vascular resistance and right-heart failure. In patients with PAH the iron-regulatory hormone hepcidin is elevated and iron homeostasis compromised. Recent research also highlights the occurrence of sub-clinical haemolysis and the presence of free haemoglobin (Hb) in PAH patients. We hypothesised, that if present on human pulmonary artery smooth cells (hPASMCs), the Hb scavenger-receptor CD163 could aid in proliferation via Hb uptake and further that expression would be modulated by stimuli of relevance to PAH. Confluent hPASMCs were challenged with increasing concentrations of hepcidin, IL-6 or Hb. RT-PCR was performed using extracted mRNA and protein expression studied by immunocytochemistry (ICC). Proliferation was measured independently by cyquant staining and BrdU incorporation. Novel findings indicate basal expression of CD163 mRNA and protein in hPASMCs. A 2-fold increase in CD163 mRNA was observed with IL-6 challenge (10ng/mL; n=3). ICC revealed minimal basal expression of CD163 that increased with hepcidin (500ng/mL) or Hb (10uM) treatment. Exposure to Hb also caused an increase in proliferation of hPASMCs by 11% (p<0.05, n=7; cyquant) or 12% (p<0.01, n=6; BrdU). This is the first report of CD163 expression and regulation in hPASMCs. Enhanced Hb uptake via CD163 may encourage iron mediated cell proliferation and novel insights into disease mechanism for PAH.

  • Pulmonary hypertension
  • Copyright ©ERS 2015
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CD163 is expressed and modulated in human pulmonary artery smooth muscle cells: Implications for pulmonary artery hypertension
Latha Ramakrishnan, Sharon Mumby, John S. Wort, Gregory J. Quinlan
European Respiratory Journal Sep 2015, 46 (suppl 59) PA4901; DOI: 10.1183/13993003.congress-2015.PA4901

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CD163 is expressed and modulated in human pulmonary artery smooth muscle cells: Implications for pulmonary artery hypertension
Latha Ramakrishnan, Sharon Mumby, John S. Wort, Gregory J. Quinlan
European Respiratory Journal Sep 2015, 46 (suppl 59) PA4901; DOI: 10.1183/13993003.congress-2015.PA4901
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