Role of FcγRI (CD64) in erythrocyte elimination and its up‐regulation in thalassaemia

Abstract

To examine any role of the high affinity Fcgamma class I receptor (FcgammaRI) (CD64) in erythrocyte elimination by mononuclear phagocytes (MP) in thalassaemia (thal), we investigated the in vitro interaction of beta-thalassaemic erythrocytes with monocytes (Mo) whose FcgammaR expression had been modulated by cytokines. Treatment of Mo with interferon (IFN)-gamma or interleukin (IL)-10 which up-regulate FcgammaRI, caused a dose-dependent increase in binding of beta-thalassaemic erythrocytes, whereas stimulation with IL-4 which down-regulates the receptor, reduced this interaction, in a dose-dependent manner, to that of normal erythrocytes. Binding of thalassaemic erythrocytes by IFN-gamma or IL-10-treated Mo was inhibited by FcgammaRI-specific reagents. In addition, Mo expression of FcgammaRI and HLA class II DR was determined by flow cytometry in Thai patients with HbH disease (alpha1/alpha2 or alpha1/Hb Constant Spring) (n = 15) or beta degrees -thal/HbE (n = 16). In both groups of patients FcgammaRI expression was increased as compared to normal controls (n = 14): mean fluorescence intensity (+/-SD) 124.79 +/- 38. 77 in HbH disease and 121.86 +/- 18.23 in beta degrees -thal/HbE versus 91.94 +/- 17.36 in normal controls (P < 0.01 and P < 0.001, respectively). In contrast, HLA class II DR expression was similar in patients and controls. The results suggest that, in thalassaemia, up-regulated FcgammaRI on mononuclear phagocytes plays a role in their interaction with erythrocytes and that this process can be modified by cytokines.

Infections in Thalassemia and Hemoglobinopathies

“…For the first two reasons, the monocyte/macrophage compartment undergoes gross hyperplasia and is hyperactive in phagocytizing all defective erythroid precursors and erythrocytes39,40,41. This increased phagocytic activity very likely reduces the capacity of the phagocytic system to defend against pathogenic microorganisms.…”

The effects of Phorbol 12-myristate 13-acetate concentration on the expression of miR-155 and miR-125b and their macrophage function-related genes in the U937 cell line

“…In this study, both miR-155 and miR-125b were higher upregulated after treatment with the lower concentration of PMA and that correlated with the increasing of phagocytic activity of macrophage. The increased phagocytic activity of macrophage may be involved in many mechanisms including the increased production of TNF-α or macrophage colony-stimulating factor (M-CSF), and the increased recognition of phosphatidylserine (PS) or IgG on target cells by macrophage (Wiener et al, 1996(Wiener et al, , 1999Banyatsuppasin et al, 2011;Wanachiwanawin et al, 1993;Chinprasertsuk et al, 1997). Therefore, from our results, at least the increased expression of TNF-α may be a mechanism that can activate phagocytic activity of U937-derived macrophage after PMA treatment.…”

Intracellular iron overload leading to DNA damage of lymphocytes and immune dysfunction in thalassemia major patients

“…Both B and T Lymphocytes are activated or stimulated usually during immune response to microbial infections . Hyperactive macrophage found in thalassemics is mainly involved in the clearance of defective erythroid precursors and this, in turn, reduces the capacity of the phagocytic system to defend against pathogenic microorganisms and might help in the progression of infections by microorganisms. Lymphoid activation observed in thalassemia cases is mainly with impaired differentiation .…”