Microglial responses after phagocytosis: Escherichia coli bioparticles, but not cell debris or amyloid beta, induce matrix metalloproteinase-9 secretion in cultured rat primary microglial cells.

Upon infection or brain damage, microglia are activated to play roles in immune responses, including phagocytosis and soluble factor release. However, little is known whether the event of phagocytosis could be a trigger for releasing soluble factors from microglia. In this study, we tested if microglia secrete a neurovascular mediator matrix metalloproteinase-9 (MMP-9) after phagocytosis in vitro. Primary microglial cultures were prepared from neonatal rat brains. Cultured microglia phagocytosed Escherichia coli bioparticles within 2 hr after incubation and started to secrete MMP-9 at around 12 hr after the phagocytosis. A TLR4 inhibitor TAK242 suppressed the E. coli-bioparticle-induced MMP-9 secretion. However, TAK242 did not change the engulfment of E. coli bioparticles in microglial cultures. Because lipopolysaccharides (LPS), the major component of the outer membrane of E. coli, also induced MMP-9 secretion in a dose-response manner and because the response was inhibited by TAK242 treatment, we assumed that the LPS-TLR4 pathway, which was activated by adhering to the substance, but not through the engulfing process of phagocytosis, would play a role in releasing MMP-9 from microglia after E. coli bioparticle treatment. To support the finding that the engulfing step would not be a critical trigger for MMP-9 secretion after the event of phagocytosis in microglia, we confirmed that cell debris and amyloid beta were both captured into microglia via phagocytosis, but neither of them induced MMP-9 secretion from microglia. Taken together, these data demonstrate that microglial response in MMP-9 secretion after phagocytosis differs depending on the types of particles/substances that microglia encountered.

Effect of Ultraviolet Irradiation on Proton Transfer Facilitated by 5,10,15,20-Tetraphenyl-21H,23H-porphine and Its Metal Complexes at a Water/1,2-Dichloroethane Interface.

We examined photochemical effects by ultraviolet irradiation on facilitated proton transfer at a water/1,2-dichloroethane (W/DCE) interface by ion-transfer voltammetry using a Xe flash lamp. 5,10,15,20-Tetraphenyl-21H,23H-porphine (H2TPP) or its metal complex, such as cobalt (Co(II)TPP), zinc (Zn(II)TPP), and nickel (Ni(II)TPP) complexes, was added into the DCE phase as an ionophore for the facilitated proton transfer. After we irradiated the W/DCE interface through the W phase, the voltammetric waves for proton transfer facilitated by H2TPP and Co(II)TPP were remarkably enhanced and shifted to the lower potential region, compared to those before irradiation. We confirmed from the pH and argentometric titrations that such enhancements and shifts of the waves were caused by hydrogen chloride (HCl) produced by photodecomposition of DCE. On the other hand, the waves for proton transfer facilitated by Zn(II)TPP and Ni(II)TPP were very small from the beginning, and showed neither enhancement nor any shift upon irradiation.