Background: Platelet-activating factor (PAF) is a potent phospholipid media
tor that plays various roles in neuronal function and brain development. Th
e production and release of PAF in the brain has also been reported under v
arious pathological conditions. However, neither the cell types and mechani
sm responsible for the synthesis of PAF nor its target cells have been full
y identified.
Results: Using primary culture cells derived from rat brain and a very sens
itive assay method for PAF, we found that PAF was synthesized in neurones f
ollowing stimulation with glutamic acid. PAF synthesis required activation
of NMDA receptors and subsequent elevation of intracellular calcium ions. M
icroglia, which express functional PAF receptors to a high level, showed a
marked chemotactic response to PAF. This chemotaxis is a receptor-mediated
process, as microglia from PAF-receptor-deficient mice did not show such a
response. The activation of a pertussis-toxin-sensitive G-protein and mitog
en-activated protein kinase presumably plays a role in intracellular signal
ling leading to chemotaxis.
Conclusions: Considering the cytoprotective and cytotoxic roles of microgli
a, PAF functions as a key messenger in neurone-microglial interactions.