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

Background: The 'high and low responder' phenomenon describes an intersubject variability in mononuclear cell (MNC) prothrombotic reactivity to lipopolysaccharide (LPS) stimulation. Because alterations in surface CD36 expression in monocytes were associated with impaired monocyte function, we studied the relationship between the levels of surface CD36 presentation and the prothrombotic reactivity of monocytes from high-responder (HR) and low-responder (LR) individuals. Methods and results: The relationship between levels of tissue factor (TF) expression and surface CD36 presentation in MNCs from HR individuals (n = 7) and LR individuals (n = 8) was investigated. Resting MNCs from HR individuals contained significantly more TF mRNA but levels of TF antigen and procoagulant activity similar to MNCs from LR individuals. Resting CD14+ MNCs from HR individuals expressed significantly lower surface CD36, as mean fluorescence intensities (MFIs) were 70.4 +/- 6.3 vs. 132.0 +/- 14.5 arbitrary units (AU) in HR and LR individuals, respectively. MFI from surface TF negatively correlated with surface CD36 in the population of resting (r = -0.598, P = 0.031) and LPS-stimulated (r = -0.672, P = 0.009) CD14+ cells. LPS-stimulated MNCs from HR individuals contained significantly more TF in a surface pool (2079 +/- 199 vs. 786 +/- 57 AU) along with higher TF procoagulant activity (57.3 +/- 15.2 vs. 21.1 +/- 4.5 mU 10(6) cells(-1)) as compared with LR individuals. CD14+ MNCs from HR individuals expressed less surface CD36 during a 2-h LPS challenge. Conclusions: A novel phenotype of monocytes characterized by high TF and low CD36 presentation could be further developed for use as a marker for detection of HR individuals prone to developing prothrombotic conditions.