The Journal of immunology : official journal of the American Association of Immunologists
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Activated microglia are thought to undergo apoptosis as a self-regulatory mechanism. To better understand molecular mechanisms of the microglial apoptosis, apoptosis-resistant variants of microglial cells were selected and characterized. The expression of lipocalin 2 (lcn2) was significantly down-regulated in the microglial cells that were resistant to NO-induced apoptosis. lcn2 expression was increased by inflammatory stimuli in microglia. ⋯ Treatment of primary microglia cultures with the rLCN2 protein also induced the deramification of microglia. The deramification of microglia was closely related with the apoptosis-prone phenotype, because other deramification-inducing agents such as cAMP-elevating agent forskolin, ATP, and calcium ionophore also rendered microglia more sensitive to cell death. Taken together, our results suggest that activated microglia may secrete LCN2 protein, which act in an autocrine manner to sensitize microglia to the self-regulatory apoptosis and to endow microglia with an amoeboid form, a canonical morphology of activated microglia in vivo.
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The reason why particular inhaled Ags induce allergic sensitization while others lead to immune tolerance is unclear. Along with a genetic predisposition to atopy, intrinsic characteristics of these Ags must be important. A common characteristic of many allergens is that they either possess proteinase activity or are inhaled in particles rich in proteinases. ⋯ Finally, we showed that PAR-2-mediated allergic sensitization was TNF-dependent. Thus, PAR-2 activation in the airways could be a critical factor in the development of allergic sensitization following mucosal exposure to allergens with serine proteinase activity. Interfering with this pathway may prove to be useful for the prevention or treatment of allergic diseases.