High tissue factor-expressing human monocytes carry low surface CD36: application to intersubject variability

Area of Science:

• Immunology
• Hematology
• Cell Biology

Background:

• The 'high and low responder' phenomenon describes variability in mononuclear cell (MNC) prothrombotic reactivity after lipopolysaccharide (LPS) stimulation.
• Altered surface CD36 expression on monocytes is linked to impaired monocyte function.

Purpose of the Study:

• To investigate the relationship between surface CD36 levels and monocyte prothrombotic reactivity in high-responder (HR) and low-responder (LR) individuals.
• To determine if CD36 expression levels correlate with tissue factor (TF) presentation and prothrombotic activity.

Main Methods:

• Compared TF mRNA, TF antigen, procoagulant activity, and surface CD36 expression in MNCs from HR and LR individuals.
• Utilized flow cytometry to measure mean fluorescence intensities (MFIs) of surface CD36 and TF on CD14+ monocytes.
• Analyzed correlations between surface TF and surface CD36 expression in resting and LPS-stimulated CD14+ cells.

Main Results:

• Resting MNCs from HR individuals had higher TF mRNA but similar TF antigen and procoagulant activity compared to LR individuals.
• Resting CD14+ monocytes from HR individuals showed significantly lower surface CD36 expression (MFI 70.4 vs. 132.0 AU).
• Surface TF negatively correlated with surface CD36 in both resting (r = -0.598) and LPS-stimulated (r = -0.672) CD14+ cells.
• LPS-stimulated MNCs from HR individuals exhibited significantly higher surface TF pools and procoagulant activity compared to LR individuals.
• CD14+ monocytes from HR individuals displayed reduced surface CD36 during LPS challenge.

Conclusions:

• A novel monocyte phenotype characterized by high TF and low CD36 presentation was identified in HR individuals.
• This phenotype may serve as a valuable marker for identifying individuals at higher risk for developing prothrombotic conditions.