CD33-Related Siglecs in Early Recognition of Tumour Cells and Viruses by Mononuclear Phagocytes

Abstract

The sialic acid binding immunoglobulin-like lectins (siglecs) comprise a family of receptors that are differentially expressed on leukocytes and other immune cells. Their molecular properties and the presence of tyrosine-based motifs suggest that they could be involved in fine-tuning the immune responses. Peripheral blood derived monocytes express siglec-3, -5, -7, -9, and -10 (1-10% monocyte population). Upon differentiation to macrophages a general trend of decrease in siglec-3, -5 and -9 and increase for siglec-7 expression was observed. The level of expression and degree of change during differentiation varied between individual donors. It is of special interest that siglec expression on mononuclear phagocytes is further regulated by different cytokines (IFN-gamma: increased siglec-1 and decrease siglec-5, -7 and -9; IL-4: increased siglec-7 and 9 and decrease siglec-1). Six month monocyte surface siglec expression analysis of the 15 volunteers revealed that, siglec-9 shows the most diverse expression pattern as compared to the other monocyte limited siglecs, and these changes in expression pattern has direct relation with serum CRP levels. Furthermore, co-culturing monocytes with viruses revealed that mere presence of viral particles affects monocyte surface siglec expression profile. In addition, the viral dose and time of incubation contribute to these changes. The alteration in the siglec expression pattern in response to pathogens/tumour cells could be part of the host defence system. K562 erythroleukemia tumour cells were able to elicit early sialic acid (Sia) dependent cytokine secretion by mononuclear phagocytes. And this early cytokine secretion by mononuclear phagocytes upon co-culture with K562 surface Sia derivatives was confirmed with real time IL-6 mRNA synthesis. Furthermore, an accumulation of siglec-7 was observed at the cellular synapses between these two cell types. As siglecs are the only Sia recognising receptors present on innate immune system cells, and they could be involved in the observed Sia mediated activation processes. Here it is shown that siglec-7 could plays an important role in controlling the Sia mediated activation of mononuclear phagocytes by K562 tumour cells, as in presence of anti siglec-7 mAb activation of mononuclear phagocytes is reduced by 30-40%.