PB0406 - Human platelets and megakaryocytes express precursor forms of neurotrophins and their respective receptors

Background: Initially discovered in the brain, neurotrophins are growth factors essential for neural development and survival. Interestingly, the Brain-Derived Neurotrophic Factor (BDNF) has been found in platelets in concentrations reaching 100-1000-fold those of neurons. Previously, we confirmed the expression of the BDNF receptor, TrkB, as well as the presence of a BDNF/TrkB signaling mechanism in platelets. The presence of other neurotrophins, i.e., nerve growth factor (NGF), neurotrophin 3 and 4 (NT3 and NT4) or their receptors (TrkA and TrkC), have not been investigated in platelets or their precursor cells, megakaryocytes.

Aims: To investigate the expression and the role of NGF, NT3, NT4 and their receptors in human platelets and megakaryocytes.

Methods: Platelets and CD34+ cells were isolated from peripheral blood obtained from healthy participants. Neurotrophins and their receptors were investigated by western blotting, flow cytometry, qPCR and ELISAs in human platelets and CD34+ derived megakaryocytes. The effect of neurotrophins on platelet function was assessed with light transmission aggregometry in washed platelets. The study received ethical approval and all participants gave informed consent.

Results: Immunoblotting showed a 80-100kDa-band, consistent with a truncated form of TrkA and TrkC, confirmed by ELISA and flow cytometry. The precursor form of the neurotrophins NGF and NT3 were detected, but mature neurotrophins were absent. Similarly to BDNF, NT4 induced platelet aggregation at concentrations acting on the TrkB receptor; neither NGF nor NT3 induced platelet aggregation.

Conclusion(s): We show that human platelets express a precursor form of NGF and NT3 as well as a truncated form of the receptors TrkA et TrkC. NGF and NT3 did not induce platelet aggregation, in contrast to BDNF and NT4 at concentrations active on the TrkB receptor. The function of the truncated TrkA and TrkC receptor in platelets and megakaryocytes remains to be elucidated.