Heterogeneity of Microglial Activation in the Innate Immune Response in the Brain

The immune response in the brain has been widely investigated and while many studies have focused on the proinflammatory cytotoxic response, the brain’s innate immune system demonstrates significant heterogeneity. Microglia, like other tissue macrophages, participate in repair and resolution processes after infection or injury to restore normal tissue homeostasis. This review examines the mechanisms that lead to reduction of self-toxicity and to repair and restructuring of the damaged extracellular matrix in the brain. Part of the resolution process involves switching macrophage functional activation to include reduction of proinflammatory mediators, increased production and release of anti-inflammatory cytokines, and production of cytoactive factors involved in repair and reconstruction of the damaged brain. Two partially overlapping and complimentary functional macrophage states have been identified and are called alternative activation and acquired deactivation. The immunosuppressive and repair processes of each of these states and how alternative activation and acquired deactivation participate in chronic neuroinflammation in the brain are discussed

Regulation of Macrophage Motility by the Water Channel Aquaporin-1: Crucial Role of M0/M2 Phenotype Switch

The water channel aquaporin-1 (AQP1) promotes migration of many cell types. Although AQP1 is expressed in macrophages, its potential role in macrophage motility, particularly in relation with phenotype polarization, remains unknown. We here addressed these issues in peritoneal macrophages isolated from AQP1-deficient mice, either undifferentiated (M0) or stimulated with LPS to orientate towards pro-inflammatory phenotype (classical macrophage activation; M1). In non-stimulated macrophages, ablation of AQP1 (like inhibition by HgCl2) increased by 2-3 fold spontaneous migration in a Src/PI3K/Rac-dependent manner. This correlated with cell elongation and formation of lamellipodia/ruffles, resulting in membrane lipid and F4/80 recruitment to the leading edge. This indicated that AQP1 normally suppresses migration of resting macrophages, as opposed to other cell types. Resting Aqp1-/- macrophages exhibited CD206 redistribution into ruffles and increased arginase activity like IL4/IL13 (alternative macrophage activation; M2), indicating a M0-M2 shift. In contrast, upon M1 orientation by LPS in vitro or peritoneal inflammation in vivo , migration of Aqp1-/- macrophages was reduced. Taken together, these data indicate that AQP1 oppositely regulates macrophage migration, depending on stimulation or not by LPS, and that macrophage phenotypic and migratory changes may be regulated independently of external cues

Trace element accumulation in plant species differently affected by abandoned tailings in the Riotinto mining district

Coarse, acidic and metal polluted substrata generated by extensive metal mining in the Riotinto area (Huelva province, SW Spain) are model habitats for biogeochemical studies and for designing plant-assisted remediation technologies. Major and trace element concentrations were determined in different plant parts from the few spontaneous species growing in areas differently impacted by abandoned mine waste: Erica andevalensis, Erica australis, Nerium oleander, Halimium ocymoides and Cistus ladanifer, in order to evaluate their potential for soil reclamation. E. andevalensis, which is an endemic species to the Iberian Pyrite Belt, forms monospecific patches in the most polluted sites and showed an asymptomatic scarcity of essential macroelements (Ca, Mg and P) in leaves. The two heathers accumulate very high concentrations of As, Cu, Fe, Pb, S and Zn in the root bark, but in their aerial parts only As and Pb (among potentially phytotoxic elements) are accumulated at higher levels than those reported for Erica species growing in unpolluted areas. Stems and leaves from N. oleander, H. ocymoides and C. ladanifer had remarkably higher Cd and Zn concentrations than those measured in E. andevalensis and E. australis. Although comparisons among plant species showed different element accumulation patterns, in general, all species have a common adaptative strategy: the selective uptake of essential elements and the exclusion of potentially phytotoxic elements. However, as the shrub E. andevalensis tolerates the most extreme edaphic conditions and its breeding and growing are compatible with local climatic conditions, it seems the most suitable species for the phytostabilization of abandoned waste in the Riotinto mining district