Erythrocyte P2X 1 receptor expression is correlated with change in haematocrit in patients admitted to the ICU with blood pathogen-positive sepsis

Crit Care. 2018 Aug 2;22(1):181. doi: 10.1186/s13054-018-2100-3.

Abstract

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.

Keywords: Anaemia; Exotoxemia/endotoxemia; Haematocrit; Haemoglobin; Haemolysis; P2X; Purinergic signalling; Sepsis; Toxins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Bacterial Toxins / blood
  • Emergency Service, Hospital / organization & administration
  • Emergency Service, Hospital / statistics & numerical data
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Gram-Negative Bacteria / enzymology
  • Gram-Negative Bacteria / pathogenicity
  • Gram-Positive Bacteria / enzymology
  • Gram-Positive Bacteria / pathogenicity
  • Hematocrit / methods*
  • Hematocrit / statistics & numerical data
  • Humans
  • Intensive Care Units / organization & administration
  • Intensive Care Units / statistics & numerical data
  • Male
  • Middle Aged
  • Prospective Studies
  • Receptors, Purinergic P2X1 / analysis*
  • Receptors, Purinergic P2X1 / blood
  • Sepsis / blood*
  • Systemic Inflammatory Response Syndrome
  • Vitamin D / analysis
  • Vitamin D / blood

Substances

  • Bacterial Toxins
  • Receptors, Purinergic P2X1
  • Vitamin D