Erythrocyte P2X 1 receptor expression is correlated with change in haematocrit in patients admitted to the ICU with blood pathogen-positive sepsis
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....
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| Veröffentlicht in: | Critical care (London, England) England), 2018-08, Vol.22 (1), p.181 |
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| creator | Fagerberg, Steen K Patel, Parth Andersen, Lars W Lui, Xiaowen Donnino, Michael W Praetorius, Helle A |
| description | 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).
Patients admitted to the ED and successively transferred to ICU with the diagnosis sepsis ( |
| doi_str_mv | 10.1186/s13054-018-2100-3 |
| format | Article |
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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 P2X
and P2X
receptor abundance using indirect flow cytometry.
Here, we find inverse correlation between P2X
receptor expression and change in haematocrit (r
- 0.80) and haemoglobin (r
- 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 P2X
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 P2X
expression (0.007 ± 0.182 and - 0.020 ± 0.058 mg/dl, respectively).
High levels of P2X
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.</description><identifier>EISSN: 1466-609X</identifier><identifier>DOI: 10.1186/s13054-018-2100-3</identifier><identifier>PMID: 30071869</identifier><language>eng</language><publisher>England</publisher><subject>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</subject><ispartof>Critical care (London, England), 2018-08, Vol.22 (1), p.181</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0002-0970-5061</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,864,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30071869$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fagerberg, Steen K</creatorcontrib><creatorcontrib>Patel, Parth</creatorcontrib><creatorcontrib>Andersen, Lars W</creatorcontrib><creatorcontrib>Lui, Xiaowen</creatorcontrib><creatorcontrib>Donnino, Michael W</creatorcontrib><creatorcontrib>Praetorius, Helle A</creatorcontrib><title>Erythrocyte P2X 1 receptor expression is correlated with change in haematocrit in patients admitted to the ICU with blood pathogen-positive sepsis</title><title>Critical care (London, England)</title><addtitle>Crit Care</addtitle><description>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).
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 P2X
and P2X
receptor abundance using indirect flow cytometry.
Here, we find inverse correlation between P2X
receptor expression and change in haematocrit (r
- 0.80) and haemoglobin (r
- 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 P2X
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 P2X
expression (0.007 ± 0.182 and - 0.020 ± 0.058 mg/dl, respectively).
High levels of P2X
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.</description><subject>Aged</subject><subject>Bacterial Toxins - blood</subject><subject>Emergency Service, Hospital - organization & administration</subject><subject>Emergency Service, Hospital - statistics & numerical data</subject><subject>Enzyme-Linked Immunosorbent Assay - methods</subject><subject>Female</subject><subject>Gram-Negative Bacteria - enzymology</subject><subject>Gram-Negative Bacteria - pathogenicity</subject><subject>Gram-Positive Bacteria - enzymology</subject><subject>Gram-Positive Bacteria - pathogenicity</subject><subject>Hematocrit - methods</subject><subject>Hematocrit - statistics & numerical data</subject><subject>Humans</subject><subject>Intensive Care Units - organization & administration</subject><subject>Intensive Care Units - statistics & numerical data</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Prospective Studies</subject><subject>Receptors, Purinergic P2X1 - analysis</subject><subject>Receptors, Purinergic P2X1 - blood</subject><subject>Sepsis - blood</subject><subject>Systemic Inflammatory Response Syndrome</subject><subject>Vitamin D - analysis</subject><subject>Vitamin D - blood</subject><issn>1466-609X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFj7tOAzEQRS0kRMLjA2jQ_IDBzgZnU0dB0KUAKV3k7A7xoF3b8gyP_Q2-GFZATXV1pHOKq9SlNdfW1u6GbWVu59rYWs-sMbo6UlM7d047s9xO1CnzizF2UbvqRE0qYxbf0XKqPtdlkFBSMwjCZrYFCwUbzJIK4EcuyEwpAjE0qRTsvGAL7yQBmuDjAYEiBI-9l9QUkhGzF8IoDL7tSUZfEkhAeFg9_aT7LqV29EI6YNQ5MQm9ITBmJj5Xx8--Y7z43TN1dbd-XN3r_Lrvsd3lQr0vw-7vRPWv8AUxv1p7</recordid><startdate>20180802</startdate><enddate>20180802</enddate><creator>Fagerberg, Steen K</creator><creator>Patel, Parth</creator><creator>Andersen, Lars W</creator><creator>Lui, Xiaowen</creator><creator>Donnino, Michael W</creator><creator>Praetorius, Helle A</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><orcidid>https://orcid.org/0000-0002-0970-5061</orcidid></search><sort><creationdate>20180802</creationdate><title>Erythrocyte P2X 1 receptor expression is correlated with change in haematocrit in patients admitted to the ICU with blood pathogen-positive sepsis</title><author>Fagerberg, Steen K ; Patel, Parth ; Andersen, Lars W ; Lui, Xiaowen ; Donnino, Michael W ; Praetorius, Helle A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-pubmed_primary_300718693</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Aged</topic><topic>Bacterial Toxins - blood</topic><topic>Emergency Service, Hospital - organization & administration</topic><topic>Emergency Service, Hospital - statistics & numerical data</topic><topic>Enzyme-Linked Immunosorbent Assay - methods</topic><topic>Female</topic><topic>Gram-Negative Bacteria - enzymology</topic><topic>Gram-Negative Bacteria - pathogenicity</topic><topic>Gram-Positive Bacteria - enzymology</topic><topic>Gram-Positive Bacteria - pathogenicity</topic><topic>Hematocrit - methods</topic><topic>Hematocrit - statistics & numerical data</topic><topic>Humans</topic><topic>Intensive Care Units - organization & administration</topic><topic>Intensive Care Units - statistics & numerical data</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Prospective Studies</topic><topic>Receptors, Purinergic P2X1 - analysis</topic><topic>Receptors, Purinergic P2X1 - blood</topic><topic>Sepsis - blood</topic><topic>Systemic Inflammatory Response Syndrome</topic><topic>Vitamin D - analysis</topic><topic>Vitamin D - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fagerberg, Steen K</creatorcontrib><creatorcontrib>Patel, Parth</creatorcontrib><creatorcontrib>Andersen, Lars W</creatorcontrib><creatorcontrib>Lui, Xiaowen</creatorcontrib><creatorcontrib>Donnino, Michael W</creatorcontrib><creatorcontrib>Praetorius, Helle A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Critical care (London, England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fagerberg, Steen K</au><au>Patel, Parth</au><au>Andersen, Lars W</au><au>Lui, Xiaowen</au><au>Donnino, Michael W</au><au>Praetorius, Helle A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Erythrocyte P2X 1 receptor expression is correlated with change in haematocrit in patients admitted to the ICU with blood pathogen-positive sepsis</atitle><jtitle>Critical care (London, England)</jtitle><addtitle>Crit Care</addtitle><date>2018-08-02</date><risdate>2018</risdate><volume>22</volume><issue>1</issue><spage>181</spage><pages>181-</pages><eissn>1466-609X</eissn><abstract>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).
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 P2X
and P2X
receptor abundance using indirect flow cytometry.
Here, we find inverse correlation between P2X
receptor expression and change in haematocrit (r
- 0.80) and haemoglobin (r
- 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 P2X
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 P2X
expression (0.007 ± 0.182 and - 0.020 ± 0.058 mg/dl, respectively).
High levels of P2X
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.</abstract><cop>England</cop><pmid>30071869</pmid><doi>10.1186/s13054-018-2100-3</doi><orcidid>https://orcid.org/0000-0002-0970-5061</orcidid></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Springer Nature OA Free Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection; SpringerLink Journals - AutoHoldings |
| subjects | 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 |
| title | Erythrocyte P2X 1 receptor expression is correlated with change in haematocrit in patients admitted to the ICU with blood pathogen-positive sepsis |
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