Title |
Human severe sepsis cytokine mixture increases β2-integrin-dependent polymorphonuclear leukocyte adhesion to cerebral microvascular endothelial cells in vitro
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Published in |
Critical Care, December 2015
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DOI | 10.1186/s13054-015-0883-z |
Pubmed ID | |
Authors |
Chris Blom, Brittany L Deller, Douglas D Fraser, Eric K Patterson, Claudio M Martin, Bryan Young, Patricia C Liaw, Payam Yazdan-Ashoori, Angelica Ortiz, Brian Webb, Greg Kilmer, David E Carter, Gediminas Cepinskas |
Abstract |
Sepsis-associated encephalopathy (SAE) is a state of acute brain dysfunction in response to a systemic infection. We propose that systemic inflammation during sepsis causes increased adhesion of leukocytes to the brain microvasculature, resulting in blood brain barrier dysfunction. Thus, our objectives were (1) to measure inflammatory analytes in plasma of severe sepsis patients to create an experimental cytokine mixture (CM), and (2) to use this CM to investigate the activation and interactions of polymorphonuclear leukocytes (PMN) and human cerebrovascular endothelial cells (hCMEC/D3) in vitro. The concentrations of 41 inflammatory analytes were quantified in plasma obtained from 20 severe sepsis patients and 20 age-/sex-matched healthy controls employing an antibody microarray. Two CMs were prepared to mimic severe sepsis (SSCM) and control (CCM), and these CMs were then used for PMN and hCMEC/D3 stimulation in vitro. PMN adhesion to hCMEC/D3 was assessed under conditions of flow (shear stress 0.7 dyn/cm(2)). Eight inflammatory analytes elevated in plasma obtained from severe sepsis patients were used to prepare SSCM and CCM. Stimulation of PMN with SSCM led to a marked increase in PMN adhesion to hCMEC/D3, as compared to CCM. PMN adhesion was abolished with neutralizing antibodies to either β2 (CD18), αL/β2 (CD11α/CD18; LFA-1) or αM/β2 (CD11β/CD18; Mac-1) integrins. In addition, immune-neutralization of the endothelial (hCMEC/D3) cell adhesion molecule, ICAM-1 (CD54) also suppressed PMN adhesion. Human SSCM up-regulates PMN pro-adhesive phenotype and promotes PMN adhesion to cerebrovascular endothelial cells through a β2-integrin-ICAM-1-dependent mechanism. PMN adhesion to the brain microvasculature may contribute to SAE. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Puerto Rico | 2 | 67% |
Unknown | 1 | 33% |
Demographic breakdown
Type | Count | As % |
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Practitioners (doctors, other healthcare professionals) | 3 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Brazil | 1 | 2% |
Unknown | 51 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 11 | 21% |
Student > Ph. D. Student | 8 | 15% |
Student > Master | 8 | 15% |
Professor | 6 | 12% |
Student > Doctoral Student | 4 | 8% |
Other | 10 | 19% |
Unknown | 5 | 10% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 6 | 12% |
Agricultural and Biological Sciences | 4 | 8% |
Immunology and Microbiology | 2 | 4% |
Business, Management and Accounting | 2 | 4% |
Other | 7 | 13% |
Unknown | 7 | 13% |