Article open access publication

Erythrocyte P2X1 receptor expression is correlated with change in haematocrit in patients admitted to the ICU with blood pathogen-positive sepsis

Critical Care, Springer Nature, ISSN 1466-609X

Volume 22, 1, 2018

DOI:10.1186/s13054-018-2100-3, Dimensions: pub.1105964063, PMC: PMC6091015, PMID: 30071869,

Authors

* Corresponding author

Affiliations

Organisations

  1. (1) Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
  2. (2) Aarhus University, grid.7048.b, AU
  3. (3) Aarhus University Hospital, grid.154185.c, Central Denmark Region

Countries

Denmark

Continents

Europe

Description

BACKGROUND: Pore-forming proteins released from bacteria or formed as result of complement activation are known to produce severe cell damage. Inhibition of purinergic P2X receptors markedly reduces damage inflicted by cytolytic bacterial toxin and after complement activation in both erythrocytes and monocytes. P2X expression generally shows variation throughout the population. Here, we investigate correlation between P2X receptor abundance in blood cell plasma membranes and haematocrit during sepsis, in patients admitted to the emergency department (ED) or intensive care unit (ICU). METHOD: Patients admitted to the ED and successively transferred to ICU with the diagnosis sepsis (< 2 systemic inflammatory response syndrome (SIRS) criteria and suspected infection), were grouped as either blood pathogen-positive (14 patients) or blood pathogen-negative (20 patients). Blood samples drawn at ICU admission were analysed for P2X1 and P2X7 receptor abundance using indirect flow cytometry. RESULTS: Here, we find inverse correlation between P2X1 receptor expression and change in haematocrit (rs - 0.80) and haemoglobin (rs - 0.78) levels from admission to ED to arrival at ICU in patients with pathogen-positive sepsis. This correlation was not found in patients without confirmed bacteraemia. Patients with high P2X1 expression had a significantly greater change in both haematocrit (- 0.59 ± 0.36) and haemoglobin levels (- 0.182 ± 0.038 mg/dl) per hour, during the first hours after hospital admission compared to patients with low P2X1 expression (0.007 ± 0.182 and - 0.020 ± 0.058 mg/dl, respectively). CONCLUSION: High levels of P2X1 are correlated with more pronounced reduction in haematocrit and haemoglobin in patients with confirmed bacteraemia. This supports previous in vitro findings of P2X activation as a significant component in cell damage caused by pore-forming bacterial toxins and complement-dependent major attack complex. These data suggest a new potential target for future therapeutics in initial stages of sepsis.

Funders

Research Categories

Main Subject Area

Fields of Research

Links & Metrics

NORA University Profiles

Aarhus University

Dimensions Citation Indicators

Times Cited: 4

Field Citation Ratio (FCR): 3.2

Relative Citation ratio (RCR): 0.51

Open Access Info

Pure Gold