| First Author | Pei Z | Year | 2007 |
| Journal | Glia | Volume | 55 |
| Issue | 13 | Pages | 1362-73 |
| PubMed ID | 17654704 | Mgi Jnum | J:156303 |
| Mgi Id | MGI:4420213 | Doi | 10.1002/glia.20545 |
| Citation | Pei Z, et al. (2007) MAC1 mediates LPS-induced production of superoxide by microglia: the role of pattern recognition receptors in dopaminergic neurotoxicity. Glia 55(13):1362-73 |
| abstractText | Microglia-derived superoxide is critical for the inflammation-induced selective loss of dopaminergic (DA) neurons, but the underlying mechanisms of microglial activation remain poorly defined. Using neuron-glia and microglia-enriched cultures from mice deficient in the MAC1 receptor (MAC1-/-), we demonstrate that lipopolysaccharide (LPS) treatment results in lower TNFalpha response, attenuated loss of DA neurons, and absence of extracellular superoxide production in MAC1-/- cultures. Microglia accumulated fluorescently labeled LPS in punctate compartments associated with the plasma membrane, intracellular vesicles, and the Golgi apparatus. Cytochalasin D (CD), an inhibitor of phagocytosis, blocked LPS internalization. However, microglia derived from Toll-like receptor 4 deficient mice and MAC1-/- mice failed to show a significant decrease in intracellular accumulation of labeled LPS, when compared with controls. Pretreatment with the scavenger receptor inhibitor, fucoidan, inhibited 79% of LPS accumulation in microglia without affecting superoxide, indicating that LPS internalization and superoxide production are mediated by separate phagocytosis receptors. Together, these data demonstrate that MAC1 is essential for LPS-induced superoxide from microglia, implicating MAC1 as a critical trigger of microglial-derived oxidative stress during inflammation-mediated neurodegeneration. |
