Effect of recombinant activated protein C and low-dose heparin on neutrophil-endothelial cell interactions in septic shock

Linda A. Kirschenbaum, Wilma S. Correa-Lopez, Patricia Ohrum, Anita Tsen, John Khazin, Mark E. Astiz

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

OBJECTIVE: To examine the effects of recombinant activated protein C (rhAPC) and low-dose heparin on neutrophil-platelet-endothelial cell interactions in septic shock. DESIGN: Controlled experiments using phase contrast microscopy to study neutrophil, platelet, and endothelial cell interactions in flowing cell suspensions under simulated physiologic conditions. SETTING: University research laboratory. PATIENTS: Adult patients with septic shock and normal volunteers. INTERVENTIONS: Neutrophils and platelets removed from control subjects were stimulated with plasma and serum from 21 patients in septic shock and perfused over endothelial cells. Activated protein C, low-dose heparin, and low-dose heparin with rhAPC were added to cells suspended in septic plasma. Neutrophil rolling velocity and the number of neutrophils adherent to endothelial cells and in aggregates were determined. Flow cytometric analysis of CD11b/CD63 cells was used to identify platelet-neutrophil aggregates. MEASUREMENTS AND MAIN RESULTS: Activated protein C significantly decreased neutrophil adhesion and aggregation and increased rolling velocity in cells stimulated with both septic serum and septic plasma. Significant decreases in platelet-neutrophil aggregates induced by septic plasma were also observed. Low-dose heparin alone had no effects on these variables. The addition of low-dose heparin to cells suspended in septic plasma and rhAPC attenuated the benefits observed with rhAPC alone in each of these variables. CONCLUSIONS: These data suggest that the in vitro addition of rhAPC decreases sepsis-induced interactions between isolated platelets, neutrophils, and endothelial cells. Low-dose heparin attenuates the benefits observed with rhAPC. The changes in neutrophil-endothelial cell interactions demonstrated with rhAPC may play a role in preserving microvascular patency in patients with septic shock.

Original languageEnglish (US)
Pages (from-to)2207-2212
Number of pages6
JournalCritical Care Medicine
Volume34
Issue number8
DOIs
StatePublished - Aug 2006
Externally publishedYes

Fingerprint

Septic Shock
Protein C
Recombinant Proteins
Cell Communication
Heparin
Neutrophils
Endothelial Cells
Blood Platelets
Phase-Contrast Microscopy
drotrecogin alfa activated
Serum
Sepsis
Suspensions
Healthy Volunteers

Keywords

  • Activated protein C
  • Endothelium
  • Heparin
  • Neutrophil
  • Platelet
  • Septic shock
  • Thrombin

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Effect of recombinant activated protein C and low-dose heparin on neutrophil-endothelial cell interactions in septic shock. / Kirschenbaum, Linda A.; Correa-Lopez, Wilma S.; Ohrum, Patricia; Tsen, Anita; Khazin, John; Astiz, Mark E.

In: Critical Care Medicine, Vol. 34, No. 8, 08.2006, p. 2207-2212.

Research output: Contribution to journalArticle

Kirschenbaum, Linda A. ; Correa-Lopez, Wilma S. ; Ohrum, Patricia ; Tsen, Anita ; Khazin, John ; Astiz, Mark E. / Effect of recombinant activated protein C and low-dose heparin on neutrophil-endothelial cell interactions in septic shock. In: Critical Care Medicine. 2006 ; Vol. 34, No. 8. pp. 2207-2212.
@article{d9f8af0b5c334b22b6c7f7a3305476a4,
title = "Effect of recombinant activated protein C and low-dose heparin on neutrophil-endothelial cell interactions in septic shock",
abstract = "OBJECTIVE: To examine the effects of recombinant activated protein C (rhAPC) and low-dose heparin on neutrophil-platelet-endothelial cell interactions in septic shock. DESIGN: Controlled experiments using phase contrast microscopy to study neutrophil, platelet, and endothelial cell interactions in flowing cell suspensions under simulated physiologic conditions. SETTING: University research laboratory. PATIENTS: Adult patients with septic shock and normal volunteers. INTERVENTIONS: Neutrophils and platelets removed from control subjects were stimulated with plasma and serum from 21 patients in septic shock and perfused over endothelial cells. Activated protein C, low-dose heparin, and low-dose heparin with rhAPC were added to cells suspended in septic plasma. Neutrophil rolling velocity and the number of neutrophils adherent to endothelial cells and in aggregates were determined. Flow cytometric analysis of CD11b/CD63 cells was used to identify platelet-neutrophil aggregates. MEASUREMENTS AND MAIN RESULTS: Activated protein C significantly decreased neutrophil adhesion and aggregation and increased rolling velocity in cells stimulated with both septic serum and septic plasma. Significant decreases in platelet-neutrophil aggregates induced by septic plasma were also observed. Low-dose heparin alone had no effects on these variables. The addition of low-dose heparin to cells suspended in septic plasma and rhAPC attenuated the benefits observed with rhAPC alone in each of these variables. CONCLUSIONS: These data suggest that the in vitro addition of rhAPC decreases sepsis-induced interactions between isolated platelets, neutrophils, and endothelial cells. Low-dose heparin attenuates the benefits observed with rhAPC. The changes in neutrophil-endothelial cell interactions demonstrated with rhAPC may play a role in preserving microvascular patency in patients with septic shock.",
keywords = "Activated protein C, Endothelium, Heparin, Neutrophil, Platelet, Septic shock, Thrombin",
author = "Kirschenbaum, {Linda A.} and Correa-Lopez, {Wilma S.} and Patricia Ohrum and Anita Tsen and John Khazin and Astiz, {Mark E.}",
year = "2006",
month = "8",
doi = "10.1097/01.CCM.0000229880.41513.86",
language = "English (US)",
volume = "34",
pages = "2207--2212",
journal = "Critical Care Medicine",
issn = "0090-3493",
publisher = "Lippincott Williams and Wilkins",
number = "8",

}

TY - JOUR

T1 - Effect of recombinant activated protein C and low-dose heparin on neutrophil-endothelial cell interactions in septic shock

AU - Kirschenbaum, Linda A.

AU - Correa-Lopez, Wilma S.

AU - Ohrum, Patricia

AU - Tsen, Anita

AU - Khazin, John

AU - Astiz, Mark E.

PY - 2006/8

Y1 - 2006/8

N2 - OBJECTIVE: To examine the effects of recombinant activated protein C (rhAPC) and low-dose heparin on neutrophil-platelet-endothelial cell interactions in septic shock. DESIGN: Controlled experiments using phase contrast microscopy to study neutrophil, platelet, and endothelial cell interactions in flowing cell suspensions under simulated physiologic conditions. SETTING: University research laboratory. PATIENTS: Adult patients with septic shock and normal volunteers. INTERVENTIONS: Neutrophils and platelets removed from control subjects were stimulated with plasma and serum from 21 patients in septic shock and perfused over endothelial cells. Activated protein C, low-dose heparin, and low-dose heparin with rhAPC were added to cells suspended in septic plasma. Neutrophil rolling velocity and the number of neutrophils adherent to endothelial cells and in aggregates were determined. Flow cytometric analysis of CD11b/CD63 cells was used to identify platelet-neutrophil aggregates. MEASUREMENTS AND MAIN RESULTS: Activated protein C significantly decreased neutrophil adhesion and aggregation and increased rolling velocity in cells stimulated with both septic serum and septic plasma. Significant decreases in platelet-neutrophil aggregates induced by septic plasma were also observed. Low-dose heparin alone had no effects on these variables. The addition of low-dose heparin to cells suspended in septic plasma and rhAPC attenuated the benefits observed with rhAPC alone in each of these variables. CONCLUSIONS: These data suggest that the in vitro addition of rhAPC decreases sepsis-induced interactions between isolated platelets, neutrophils, and endothelial cells. Low-dose heparin attenuates the benefits observed with rhAPC. The changes in neutrophil-endothelial cell interactions demonstrated with rhAPC may play a role in preserving microvascular patency in patients with septic shock.

AB - OBJECTIVE: To examine the effects of recombinant activated protein C (rhAPC) and low-dose heparin on neutrophil-platelet-endothelial cell interactions in septic shock. DESIGN: Controlled experiments using phase contrast microscopy to study neutrophil, platelet, and endothelial cell interactions in flowing cell suspensions under simulated physiologic conditions. SETTING: University research laboratory. PATIENTS: Adult patients with septic shock and normal volunteers. INTERVENTIONS: Neutrophils and platelets removed from control subjects were stimulated with plasma and serum from 21 patients in septic shock and perfused over endothelial cells. Activated protein C, low-dose heparin, and low-dose heparin with rhAPC were added to cells suspended in septic plasma. Neutrophil rolling velocity and the number of neutrophils adherent to endothelial cells and in aggregates were determined. Flow cytometric analysis of CD11b/CD63 cells was used to identify platelet-neutrophil aggregates. MEASUREMENTS AND MAIN RESULTS: Activated protein C significantly decreased neutrophil adhesion and aggregation and increased rolling velocity in cells stimulated with both septic serum and septic plasma. Significant decreases in platelet-neutrophil aggregates induced by septic plasma were also observed. Low-dose heparin alone had no effects on these variables. The addition of low-dose heparin to cells suspended in septic plasma and rhAPC attenuated the benefits observed with rhAPC alone in each of these variables. CONCLUSIONS: These data suggest that the in vitro addition of rhAPC decreases sepsis-induced interactions between isolated platelets, neutrophils, and endothelial cells. Low-dose heparin attenuates the benefits observed with rhAPC. The changes in neutrophil-endothelial cell interactions demonstrated with rhAPC may play a role in preserving microvascular patency in patients with septic shock.

KW - Activated protein C

KW - Endothelium

KW - Heparin

KW - Neutrophil

KW - Platelet

KW - Septic shock

KW - Thrombin

UR - http://www.scopus.com/inward/record.url?scp=33748121400&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748121400&partnerID=8YFLogxK

U2 - 10.1097/01.CCM.0000229880.41513.86

DO - 10.1097/01.CCM.0000229880.41513.86

M3 - Article

C2 - 16775572

AN - SCOPUS:33748121400

VL - 34

SP - 2207

EP - 2212

JO - Critical Care Medicine

JF - Critical Care Medicine

SN - 0090-3493

IS - 8

ER -