Inducible expression of macrophage receptor Marco by dendritic cells following phagocytic uptake of dead cells uncovered by oligonucleotide arrays

The efficient Ag presenting and immunostimulatory capacity of dendritic cells (DCs) has led to the use of tumor Ag-pulsed DCs in treatment regimens for cancer. Although vaccine studies involving tumor lysate-pulsed DCs have been performed, little, if any, information is available on the effects of phagocytic uptake of tumor lysate on DC biology and function. We have investigated gene expression pattern differences between unpulsed DO and tumor lysate-pulsed-DCs, using Affymetrix MG-U74Av2 oligonucleotide arrays, which contain similar to12,000 genes and expressed sequence tags. Upon 24 h tumor lysate pulsing, the levels of 87 transcripts increased at least 3-fold while the levels of 121 transcripts-were reduced by one-third or more, with accompanying p values <0.01. Most of these genes encoded proteins important for DC effector functions including cytokines, chemokines, and receptors, such as IL-12p40, macrophage inflammatory protein-2, and IL-6; Ag presentation, such as carboxypeptidase D and H2-DM; cell adhesion (e.g., EGF-fike module containing, mucin-like, hormone receptor-like sequence 1, rhoB); and T cell activation. Interestingly, we observed a high level of expression of a novel member of the class A scavenger receptor family, macrophage receptor with collagenous structure (Marco). Marco is thought to play an important role in the immune response by mediating binding and phagocytosis, but also in the formation of lamellipodia-like structures and of dendritic processes. Therefore, we have identified a repertoire of genes that likely play a role in DC function.