Interaction between neurone and microglia mediated by platelet-activating factor.
BACKGROUND
Platelet-activating factor (PAF) is a potent phospholipid mediator that plays various roles in neuronal function and brain development. The production and release of PAF in the brain has also been reported under various pathological conditions. However, neither the cell types and mechanism responsible for the synthesis of PAF nor its target cells have been fully identified.


RESULTS
Using primary culture cells derived from rat brain and a very sensitive assay method for PAF, we found that PAF was synthesized in neurones following stimulation with glutamic acid. PAF synthesis required activation of NMDA receptors and subsequent elevation of intracellular calcium ions. Microglia, 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 mitogen-activated protein kinase presumably plays a role in intracellular signalling leading to chemotaxis.


CONCLUSIONS
Considering the cytoprotective and cytotoxic roles of microglia, PAF functions as a key messenger in neurone-microglial interactions.
Aihara
M
M
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Tokyo, Tokyo 113-0033, and CREST of Japan Science and Technology Incorporation, Japan.
Ishii
S
S
Kume
K
K
Shimizu
T
T
D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D010972:Platelet Activating Factor / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000502:physiology; D051381:Rats; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled
D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor