Portal de Periódicos da CAPES

P2‐196: HEME AND HEMOGLOBIN SUPPRESS AMYLOID BETA‐MEDIATED ASTROCYTE IMMUNE FUNCTION

2018; Wiley; Volume: 14; Issue: 7S_Part_14 Linguagem: Inglês

10.1016/j.jalz.2018.06.883

1552-5279

Sitara B. Sankar, Rebecca K. Donegan, Kajol Shah, Amit R. Reddi, Levi B. Wood,

Tryptophan and brain disorders

Glial immune activity is an important aspect of Alzheimer's disease (AD) pathology. The blood factors heme and hemoglobin (Hb) are elevated in AD tissues, have immunomodulatory roles, and are known to physically bind AD hallmark protein, amyloid beta, (Aβ). Therefore, we sought to interrogate their roles in modulating Aβ mediated inflammatory activation of astrocytes, one of the primary immune cells of the brain. Primary mouse astrocytes were harvested from postnatal day 0-1 CD1 mice and conditioned with combinations of 50 nM heme, Hb, and Aβ1-42. Cytokine expression into culture medium was analyzed using a multiplexed immunoassay (EMD Millipore). Western blot, immunocytochemistry, and phagocytosis assays were performed to quantify astrocyte scavenger activity. Size exclusion chromatography was used to identify and isolate heme and Hb bound Aβ1-42 species. Our work revealed that heme and Hb suppressed immune activity of primary mouse astrocytes. Both heme and Hb significantly reduced expression of a panel of inflammatory cytokines which was upregulated by Aβ1-42 (p<0.01). Furthermore, both heme and Hb suppressed scavenger activity of astrocytes, as seen by decreased expression of the scavenger receptor CD36 (p 75kDa), Aβ1-42 oligomeric species is primarily responsible for astrocyte activation and that heme or Hb association with these oligomers reverses inflammation. Our data indicated that heme and Hb are potent modulators of astrocyte immune activity and suppress a number of critical immune functions, including the ability to clear pathogens such as Aβ.