Human ApoA-I overexpression diminishes LPS-induced systemic inflammation and multiple organ damage in mice

Emerging Roles of Apolipoprotein E and Apolipoprotein A-I in the Pathogenesis and Treatment of Lung Disease

“…For example, neutrophil recruitment to the lung is increased in Apoa1-deficient mice after LPS inhalation (28). Administration of purified human apoA-I or an adenoviral vector that expressed human apoA-I to mice challenged with LPS or lipoteichoic acid, a cell wall component of grampositive bacteria, protected against LPSinduced ALI, renal and liver injury, and mortality (77)(78)(79)(80)(81). In addition, apoA-I reduced BALF cytokines (e.g., TNF-a, IL-1b, IL-6) and TLR4 expression by vascular endothelial cells.…”

HDL in Infectious Diseases and Sepsis

“…ApoA-I in fact can directly inactivate bacterial endotoxin by protein-protein interaction (Emancipator et al 1992), being the C-terminal half of apoA-I the main domain responsible for LPS neutralization (Henning et al 2011), but also inhibits LPS-induced cytokine release from human monocytes (Flegel et al 1993); in addition, apoA-I reduces TNF-α levels during LPS challenge in rats and increases the survival rates (Humphries et al 2006), suggesting that apoA-I might inhibit LPS binding to macrophages thus inhibiting the production of inflammatory cytokines that are related to sepsis. In mice, the overexpression of apoA-I (that results in an increased serum level of both apoA-I and HDL) attenuates LPS-induced acute injury in lung and kidney (Li et al 2008); LPS-induced proinflammatory cytokines decrease, as well as CD14 expression in liver and lung, resulting in a protective effect against systemic inflammation and multiple organ damage (Li et al 2008). Similar to what reported in mice, subjects with low plasma HDL levels (hypoalphalipoproteinemia) present an increased prevalence of classical CD14++/CD16À but not of intermediate CD14++/CD16+ monocytes, further linking HDL-to LPS-mediated responses (Sala et al 2013).…”

Proteomic diversity of high density lipoproteins: our emerging understanding of its importance in lipid transport and beyond

“…HDL can also deactivate particular oxidized phospholipids accumulating in macrophages that have been infected with Mycobacterium leprae , the organism that causes leprosy ( 65 ). Similarly, HDL components can neutralize toxins released during infection, including enterohemolysin ( 66 ), LPS, and lipoteichoic acid (67)(68)(69)(70)(71). This sequestration prevents the activation of toll-like receptors (TLR) on macrophages and their subsequent secretion of proinfl ammatory cytokines (for a more in-depth review on the role of HDL in innate immunity, see Ref.…”