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Enhanced expression of cell-specific surface antigens on endothelial microparticles in sepsis-induced disseminated intravascular coagulation.

Matsumoto H, Yamakawa K, Ogura H, Koh T, Matsumoto N, Shimazu T - Shock (2015)

Bottom Line: Sepsis-induced disseminated intravascular coagulation (DIC) is a major cause of death in patients admitted to intensive care units.Endothelial injury with microparticle production is reported in the pathogenesis of sepsis.Numbers of the three antigen-positive EMPs were increased significantly in severe sepsis patients versus those in healthy controls and with the increase of ISTH DIC score, suggesting that the specific bioactivity of each antigen-positive EMP may play a role in the progression of sepsis-induced DIC.

View Article: PubMed Central - PubMed

Affiliation: *Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine; and †Laboratory for Clinical Investigation, Osaka University Hospital, Osaka, Japan.

ABSTRACT
Sepsis-induced disseminated intravascular coagulation (DIC) is a major cause of death in patients admitted to intensive care units. Endothelial injury with microparticle production is reported in the pathogenesis of sepsis. Endothelial microparticles (EMPs) present several cell-specific surface antigens with different bioactivities, for example, tissue factor (TF), thrombomodulin (TM), and endothelial protein C receptor (EPCR). We investigated associations between these three different surface antigen-positive EMPs and sepsis-induced DIC. This cross-sectional study composed of 24 patients with sepsis and 23 healthy controls was conducted from November 2012 to September 2013. Blood samples were collected from patients within 24 h of diagnosis of severe sepsis and from healthy controls. Numbers of TF-positive EMPs (TF EMPs), TM-positive EMPs (TM EMPs), and EPCR-positive EMPs (EPCR EMPs) were measured by flow cytometry immediately thereafter. Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores were assessed in the severe sepsis patients at enrollment. We assessed DIC with the International Society of Thrombosis and Haemostasis (ISTH) overt DIC diagnostic criteria algorithm. Numbers of antigen-positive EMPs were increased significantly in both severe sepsis patients and controls and with the increase in ISTH DIC score. Numbers of TF EMPs and EPCR EMPs correlated significantly with Sequential Organ Failure Assessment score, and numbers of EPCR EMPs correlated significantly with Acute Physiology and Chronic Health Evaluation II score. Numbers of the three antigen-positive EMPs were increased significantly in severe sepsis patients versus those in healthy controls and with the increase of ISTH DIC score, suggesting that the specific bioactivity of each antigen-positive EMP may play a role in the progression of sepsis-induced DIC.

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Representative flow cytometry dot plots of TF+ EMPs in a healthy control subject (A) and a patient with severe sepsis (B). The TF+ EMPs are distinctly immunostained positive for annexin V antibody, anti-CD146 antibody, and anti-CD142 antibody, shown in area Q2 indicated by the ellipse. The counts of TF+ EMPs in the blood are higher in the patient with severe sepsis than in the healthy control subject.
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Figure 1: Representative flow cytometry dot plots of TF+ EMPs in a healthy control subject (A) and a patient with severe sepsis (B). The TF+ EMPs are distinctly immunostained positive for annexin V antibody, anti-CD146 antibody, and anti-CD142 antibody, shown in area Q2 indicated by the ellipse. The counts of TF+ EMPs in the blood are higher in the patient with severe sepsis than in the healthy control subject.

Mentions: Endothelial microparticles were defined as events detected as annexin V+/CD146+ as previously described (9). Tissue factor–positive EMPs (TF+ EMPs), TM-positive EMPs (TM+ EMPs), and EPCR-positive EMPs (EPCR+ EMPs) were defined as events detected by annexin V+/CD146+/CD142+, annexin V+/CD146+/CD141+, and annexin V+/CD146+/CD201+, respectively. Endothelial microparticles were further defined as MPs having a calibrated diameter of 0.1 to approximately 2.0 μm on the basis of previous reports (9, 21). We excluded high-intensity signals caused by antibody aggregation from the flow cytometry analysis. The formation of MPs is expressed as the number of EMPs (Fig. 1).


Enhanced expression of cell-specific surface antigens on endothelial microparticles in sepsis-induced disseminated intravascular coagulation.

Matsumoto H, Yamakawa K, Ogura H, Koh T, Matsumoto N, Shimazu T - Shock (2015)

Representative flow cytometry dot plots of TF+ EMPs in a healthy control subject (A) and a patient with severe sepsis (B). The TF+ EMPs are distinctly immunostained positive for annexin V antibody, anti-CD146 antibody, and anti-CD142 antibody, shown in area Q2 indicated by the ellipse. The counts of TF+ EMPs in the blood are higher in the patient with severe sepsis than in the healthy control subject.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4418778&req=5

Figure 1: Representative flow cytometry dot plots of TF+ EMPs in a healthy control subject (A) and a patient with severe sepsis (B). The TF+ EMPs are distinctly immunostained positive for annexin V antibody, anti-CD146 antibody, and anti-CD142 antibody, shown in area Q2 indicated by the ellipse. The counts of TF+ EMPs in the blood are higher in the patient with severe sepsis than in the healthy control subject.
Mentions: Endothelial microparticles were defined as events detected as annexin V+/CD146+ as previously described (9). Tissue factor–positive EMPs (TF+ EMPs), TM-positive EMPs (TM+ EMPs), and EPCR-positive EMPs (EPCR+ EMPs) were defined as events detected by annexin V+/CD146+/CD142+, annexin V+/CD146+/CD141+, and annexin V+/CD146+/CD201+, respectively. Endothelial microparticles were further defined as MPs having a calibrated diameter of 0.1 to approximately 2.0 μm on the basis of previous reports (9, 21). We excluded high-intensity signals caused by antibody aggregation from the flow cytometry analysis. The formation of MPs is expressed as the number of EMPs (Fig. 1).

Bottom Line: Sepsis-induced disseminated intravascular coagulation (DIC) is a major cause of death in patients admitted to intensive care units.Endothelial injury with microparticle production is reported in the pathogenesis of sepsis.Numbers of the three antigen-positive EMPs were increased significantly in severe sepsis patients versus those in healthy controls and with the increase of ISTH DIC score, suggesting that the specific bioactivity of each antigen-positive EMP may play a role in the progression of sepsis-induced DIC.

View Article: PubMed Central - PubMed

Affiliation: *Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine; and †Laboratory for Clinical Investigation, Osaka University Hospital, Osaka, Japan.

ABSTRACT
Sepsis-induced disseminated intravascular coagulation (DIC) is a major cause of death in patients admitted to intensive care units. Endothelial injury with microparticle production is reported in the pathogenesis of sepsis. Endothelial microparticles (EMPs) present several cell-specific surface antigens with different bioactivities, for example, tissue factor (TF), thrombomodulin (TM), and endothelial protein C receptor (EPCR). We investigated associations between these three different surface antigen-positive EMPs and sepsis-induced DIC. This cross-sectional study composed of 24 patients with sepsis and 23 healthy controls was conducted from November 2012 to September 2013. Blood samples were collected from patients within 24 h of diagnosis of severe sepsis and from healthy controls. Numbers of TF-positive EMPs (TF EMPs), TM-positive EMPs (TM EMPs), and EPCR-positive EMPs (EPCR EMPs) were measured by flow cytometry immediately thereafter. Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores were assessed in the severe sepsis patients at enrollment. We assessed DIC with the International Society of Thrombosis and Haemostasis (ISTH) overt DIC diagnostic criteria algorithm. Numbers of antigen-positive EMPs were increased significantly in both severe sepsis patients and controls and with the increase in ISTH DIC score. Numbers of TF EMPs and EPCR EMPs correlated significantly with Sequential Organ Failure Assessment score, and numbers of EPCR EMPs correlated significantly with Acute Physiology and Chronic Health Evaluation II score. Numbers of the three antigen-positive EMPs were increased significantly in severe sepsis patients versus those in healthy controls and with the increase of ISTH DIC score, suggesting that the specific bioactivity of each antigen-positive EMP may play a role in the progression of sepsis-induced DIC.

Show MeSH
Related in: MedlinePlus