3 research outputs found
CD40L is selectively expressed on platelets from thrombocytopenic septic patients
Introduction It has been recently hypothesized that septic microangio-
pathy is caused or at least promoted by the interaction between endo-
thelial surface receptor CD40 and its ligand CD40L, expressed by activated
platelets. This interaction produces procoagulative changes in endothelial
cells, endothelial apoptosis, subendothelial matrix exposition and microthrombi formation. Since virtually all septic patients show a certain degree of coagulation abnormalities, we hypothesized that low platelet count is associated with a diff erent degree of CD40L expression and that this could correlate with the severity of disease.
Methods To determine the infl uence of sepsis on levels of platelet-derived
CD40L expression, we performed a prospective observational study in a
polyvalent university hospital ICU. Eighteen consecutively septic patients
were enrolled in the study, independently of the platelet count and the severity of disease (SOFA score). Flow cytometry of fresh blood from septic
patients (n = 18) and age-matched controls (n = 8) was performed for membrane-bound CD40L and CD62P on circulating platelets.
Results Flow cytometry demonstrated low levels of CD62P in controls
while the levels in patients were high. CD40L+ platelets were selectively
found from patients with thrombocytopenia (platelet count ≤60,000/mm3). Furthermore a direct correlation between CD40L expression and the SOFA score was found in patients with sepsis and thrombocytopenia compared to patients with sepsis without thrombocytopenia.
Conclusions These results suggest that CD40L expression on platelets is
somehow related to the degree of thrombocytopenia and possibly can
be a marker of the severity of sepsis. Although the role of endothelial-
derived CD40/platelet-derived CD40L interaction is not fully understood
during sepsis, the expression of CD40L on platelets could be related to
the severity of organ disease due to the possible bursting of endothelial
damage through this pathway. Further investigation is needed to
determine whether platelets CD40L contributes to endothelial and
subsequent organ damage, its role in thrombocytopenia and its correlation with the outcome of sepsis. The microvascular injury seems to be a central event in sepsis, so understanding the mechanisms
underlying its development is crucial for the individuation of new and
specifi c therapeutic strategies