Evolution of the haemorrhage‐associated macrophage in Cardiopulmonary bypass

Investigators & Affiliations:

Kim R Quimby¹, Andre R Greenidge¹, Anthony Harris², R Clive Landis¹.

1 Chronic Disease Research Centre, Tropical Medicine Research Institute, The University of the West Indies, Bridgetown, Barbados
2 Queen Elizabeth Hospital, Barbados

Funding:

Start Date:

Jan 2008

End Date:

January 2010

Rationale:

The traditional macrophage is identified phenotypically by low expression of the haemoglobin‐scavenging receptor CD163 but high expression of the pro‐inflammatory marker HLA‐DR. Following a haemorrhagic insult, the expression of these identifying markers becomes reversed, a phenotype recognised as the haemorrhage‐associated macrophage (HMac). This paradigm was initially described in atherosclerotic plaques, where the HMac were localized to haemorrhagic areas and provide protection from the pro‐oxidant heme. This is achieved via the hemoglobin scavenging pathway which includes the capture of free haemoglobin by plasma haptoglobin (Hp) before the complex is recognised by surface CD163 and broken down by intracellular heme‐oxygenase‐1 (HO‐1).

Considering that intravascular haemolysis is a consequence of cardiopulmonary bypass, we hypothesized that an equivalent compensatory HMac phenotype will evolve in circulating monocytes during surgery.

Methods:

This was a longitudinal study where blood samples were collected from participants at pre‐determined time‐points before, during and after the surgery. Surface CD163 and HLA‐DR expression, and intracellular HO‐1 content on the CD14pos monocytes were analysed by flow cytometry. Hp concentration was determined by ELISA.

Main Results:

There was a commitment of the monocyte population towards the protective HLADRlowCD163high phenotype. This peaked at 24hrs post‐surgery and returned to the traditional phenotype by day5 post‐surgery. During that time‐line, there was temporary consumption of Hp, reaching a nadir at 2hrs intra‐operatively and increasing again post‐operatively.

Expected impact:

These biomarkers may provide additional methods for monitoring the inflammatory response to CPB‐ induced haemolysis.

Next Steps / Future Plans:

The next plan was to investigate the representation of the haemorrhage‐associated macrophage in a chronic haemolytic disease – Sickle cell disease