To examine any role of the high affinity Fc gamma class I receptor (Fc gamm
a RI) (CD64) in erythrocyte elimination by mononuclear phagocytes (MP) in t
halassaemia (thal), we investigated the in vitro interaction of beta-thalas
saemic erythrocytes with monocytes (Mo) whose Fc gamma R expression had bee
n modulated by cytokines.
Treatment of Mo with interferon (IFN)-gamma or interleukin (IL)-10 which up
-regulate Fc gamma RI, caused a dose-dependent increase in binding of beta-
thalassaemic erythrocytes, whereas stimulation with IL-4 which down-regulat
es the receptor, reduced this interaction, in a dose-dependent manner, to t
hat of normal erythrocytes. Binding of thalassaemic erythrocytes by IFN-gam
ma or IL-10-treated Mo was inhibited by Fc gamma RI-specific reagents. In a
ddition, Mo expression of Fc gamma RI and HLA class II DR was determined by
flow cytometry in Thai patients with HbH disease (alpha(1)/alpha(2) or alp
ha(1)/Hb Constant Spring) (n = 15) or beta degrees-thal/HbE (n = 16). In bo
th groups of patients Fc gamma RI expression was increased as compared to n
ormal 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 91.9
4 +/- 17.36 in normal controls (P < 0.01 and P < 0.001, respectively). In c
ontrast, HLA class II DR expression was similar in patients and controls.
The results suggest that, in thalassaemia, up-regulated Fc gamma RI on mono
nuclear phagocytes plays a role in their interaction with erythrocytes and
that this process can be modified by cytokines.