Predominant Expression of Platelet-Activating Factor Receptor in the Rat Brain Microglia

Abstract

Cellular localization of platelet-activating factor (PAF) receptor in the rat brain was determined by (1) in situ hybridization, (2) Northern blot analysis in primary cell cultures of neurons, microglia, astrocytes, and fibroblasts, and (3) Ca2+ imaging in hippocampal culture. In situ hybridization revealed that the PAF receptor mRNA is expressed intensely in microglia and moderately in neurons. Northern blot analysis revealed that PAF receptor mRNA is the most abundant in microglia. In primary hippocampal cultures, PAF elevated intracellular Ca2+ concentration in microglia and also in neurons, but to a lesser extent. These results suggest predominant presence of PAF receptor in microglia. Cultured microglia also expressed cPLA2 mRNA the most intensely. PAF-activated microglia released arachidonic acid in a Ca(2+)-dependent manner and without conversion to its derivatives. We propose that microglia as well as neurons contribute to PAF-related events in the CNS by releasing arachidonic acid.

Interaction between neurone and microglia mediated by platelet‐activating factor

“…We also reported that arachidonic acid is released from these cells (Mori et al 1996). In the present study, we found that PAF causes a prominent chemotactic response in the activated microglia (Fig.…”

“…Taken together, these observations strongly suggest that PAF plays crucial roles in the central nervous system. We previously reported that PAFR is present in the brain (Bito et al 1992;Mori et al 1996) and stimulates intracellular increases in calcium and arachidonic acid release in microglia (Mori et al 1996). Also consistent with a role for PAF in the brain, investigators have demonstrated the stimulation of PAF synthesis in the presence of acetylcholine (Sogos et al 1990) or dopamine (Bussolino et al 1986), as well as during convulsant electrical stimuli (Kumar et al 1988), ischaemia (Baker & Chang 1993,1994Kunievsky & Yavin 1994;Francescangeli et al 1996) or viral infection (Gelbard et al 1994;.…”

Inhibition of store‐operated Ca2+ influx by acidic extracellular pH in cultured human microglia

“…ATP has been deemed a putative signaling agent released by neurons after cellular damage and may serve as an activating factor for microglia (Norenberg et al, 1994). PAF has also been suggested as an activating factor for microglia (Mori et al, 1996) and is synthesized in the brain by glia, neurons, endothelial cells, and blood-borne leukocytes after ischemic injury (Yue et al, 1994). PAF has also been indicated to have an important role in mediating CNS injury.…”

“…PAF has also been indicated to have an important role in mediating CNS injury. Mori et al (1996) have reported that PAF is able to induce arachidonic acid metabolism in microglia, potentially resulting in the production of neurotoxic factors.…”

Activation of purinergic P2X receptors inhibits P2Y-mediated Ca2+ influx in human microglia

“…However, recent work has documented a diversity of agents which cause transient increases in levels of cytoplasmic Ca 2+ in rodent microglia; such responses may be involved in coupling activating stimuli to particular cellular functions. Among the spectrum of stimuli found to elicit transient Ca 2+ responses in cultured rodent cells are complement [1], ATP [2][3][4], carbachol [5], platelet-activating factor (PAF [6]) and endothelin [7]. All of these stimuli (complement has not yet been tested) have also been found to cause transient Ca 2+ responses in human microglia [8][9][10][11].…”