Inhibition of Triggering Receptor Expressed on Myeloid Cells 1 Ameliorates Inflammation and Macrophage and Neutrophil Activation in Alcoholic Liver Disease in Mice

Tornai, David; Furi, Istvan; Shen, Zu T.; Sigalov, Alexander B.; Coban, Sahin; Szabo, Gyongyi

Further, our present study demonstrates that GF9-HDL and GA/E31-HDL exhibit not only similar macrophage uptake in vitro largely driven by SR-A ( Fig. 7) but also similar therapeutic effect in a mouse model of ALD (Figs. 1-2 ). This is in line with our previous studies where GF9-HDL and GA/E31-HDL exhibited similar therapeutic activities in cancer and arthritic mice. (16, 17) We suggest that SR-A epitopes are similarly exposed on GA31 and GE31 in GA/ E31-HDL and on PA22 and PE22 in GF9-HDL, providing similar uptake of these complexes and as a result delivery of TREM-1 inhibitory GF9 peptide sequences in vivo. The use of GA/E31-HDL in the further development of effective and low-toxicity therapy for ALD is advantageous because it makes the entire manufacturing process easier and less expensive. We also suggest that the in vitro macrophage uptake assay can be potentially used to predict the outcomes for macrophage-targeted TREM-1 therapy in vivo.