Inflammatory cytokines down-regulate CD47 specifically in CD34⁺CD38⁻ cells to induce engulfment by macrophages. (A) Serum levels of M-CSF, IL-6, TNF-α, and IFN-γ from in patients by ELISA. These cytokines were extremely high in HLH samples compared with healthy controls. *P < .01; **P < .05 by conventional t test. (B) Changes of CD47 expression levels in normal CD34⁺CD38⁻ HSCa and CD34⁺CD38⁺ progenitor cells in the presence of inflammatory cytokines. CD47 expression index represents the relative surface CD47 level calculated as median CD47 levels of analyzed cells/those in normal blood mononuclear cells. The HSC fraction, but not the progenitor fraction, showed down-regulated CD47 in response to cytokines. **P < .05 by conventional t test. (C) Suppression of CD47 in CD34⁺CD38⁻ cells by graded doses of inflammatory cytokines. The concentration of inflammatory cytokines is shown on the right. (D) Engulfment of HSCs by macrophages in response to reduction of CD47 expression by cytokines in vitro. The CD47 expression index was inversely correlated with phagocytosis index. The bar shows the regression line; the coefficient of correlation value was −0.89.