Effect of Serum Deprivation Stress on Signal Induction Regulatory Protein-Alpha (SIRP-Alpha)-Mediated Erythrophagocytosis by Macrophages
Zakaria Hindi, AbdAllah Gad, Courtney Jarvis, Talal Zahoor, Craig Spellman, Stephanie Filleur
Department of Internal Medicine, Texas Tech University Health Sciences Center, Odessa, TX, USA
Med Sci Monit Basic Res 2019; 25:100-106
Available online: 2019-03-21
Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome that involves loss of macrophages’ self-cells recognition resulting in auto-phagocytosis of erythrocytes, leukocytes, and platelets and leading to multi-system effects. The pathogenesis of HLH is unclear but can be explained by malfunction of the physiologic inhibitory pathway through interaction between macrophage SIRP-α and erythrocyte CD 47. The goal of the present study was to evaluate if erythrocytes phagocytosis occurs as a result of altered macrophage SIRP-α expression during inflammatory/stressful conditions as seen in HLH.
MATERIAL AND METHODS: RAW264.7 macrophages were cultured in serum-free media (SFM) and complete media (CM) to simulate stressful and physiologic conditions, respectively. CD47+ mouse erythrocytes were used to test interactions with macrophages at different stages. SIRP-α expressions and phagocytosis assays were measured and analyzed at different steps. The study was in vitro and used murine cells to simulate in vivo human interactions.
RESULTS: SIRP-α expressions and phagocytosis rates were higher in SFM compared to CM. Interestingly, after adding SIRP-α blocking antibodies (Ab), phagocytosis rates significantly decreased.
CONCLUSIONS: Serum deprivation and LPS/INF-Gamma induction resulted in increased SIRP-α expression and erythrophagocytosis. Using SIRP-α Ab during this condition decreased the rate of erythrophagocytosis, which indicates that SIRP-α receptor can have pro-phagocytic activity.
Keywords: Lymphohistiocytosis, Hemophagocytic, Macrophages