Role of FcgammaRI (CD64) in erythrocyte elimination and its up-regulation in thalassaemia.
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.
Wiener
E
E
Department of Haematology, Imperial College School of Medicine, St Mary's Campus, London. e.wiener@ic.ac.uk
Allen
D
D
Porter
R J
RJ
Wickramasinghe
S N
SN
Porter
J B
JB
Chinprasertsuk
S
S
Siripanyaphinyo
U
U
Pattanapanyasat
K
K
Fucharoen
S
S
Wanachiwanawin
W
W
D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism; D010587:Phagocytosis / Q000502:physiology; D017452:Receptors, IgG / Q000502:physiology*; D015854:Up-Regulation; D017086:beta-Thalassemia / Q000097:blood*
D017452:Receptors, IgG; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma