Changes in monocytic expression of aminopeptidase N/CD13 after major trauma

Abstract

SUMMARYHLA-DR expression on monocytes as marker for monocytic function is severely depressed after major trauma. The membrane enzyme aminopeptidase N/CD13 can trigger help in antigen processing by MHC class II molecules of antigen-presenting cells. We determined the simultaneous expression of HLA-DR and CD13 on peripheral blood monocytes of patients with major trauma (injury severity score of ≥ 16). 1 : 1 conjugates of phycoerythrin (PE)-to-monoclonal antibody were used in combination with QuantiBRITE TM PE beads for a standardized quantification in terms of antibodies bound per cell (ABC). The very low expression of HLA-DR antigen on monocytes of patients at day 1 after major trauma confirmed previous results in the literature. Monocytic HLA-DR expression increased slowly to reach values in the lower range of healthy volunteers at day 14. Monocytic CD13 expression at day 1 showed values in the range of healthy volunteers, and a strong rise afterwards. Fourteen days after trauma, the monocytic expression of CD13 was still much higher than in the control group. Because lipopolysaccharide (LPS) and the anti-inflammatory cytokine interleukin (IL)-10 have been shown to be involved in the depressed HLA-DR expression on monocytes in trauma patients, we studied the in vitro effects of LPS and interleukin (IL)-10 on the expression of CD13 on monocytes prepared from the peripheral blood of healthy volunteers. Whereas a 3-day IL-10 treatment resulted in a down-regulation of both HLA-DR and CD13 expression on monocytes, LPS caused a down-regulation of HLA-DR but a rapid up-regulation of CD13 levels. Therefore we suggest that, with respect to monocytic CD13 expression, LPS rather than IL-10 could well be the explanation for monocytic surface molecules after severe injury, although other mediators with a CD13 regulating function have to be considered.

CD13 Restricts TLR4 Endocytic Signal Transduction in Inflammation

“…these possibilities by molecular mapping and mutation of the CD13/TLR4 interacting domains to determine whether disrupting the interaction impacts endocytosis of TLR4 or MR as well as identifying other additional CD13-interacting proteins by proteomic analysis. In addition, we and others (27) find that CD13 expression levels are remarkably upregulated by inflammatory activation signals and tissue damage, supporting the notion that a high level of CD13 expression is important during the immune response. Understanding the contribution of these and other CD13-mediated mechanisms to endocytosis is the subject of active investigation in our laboratory.…”

“…In an effort to uncover potential clues into the mechanism by which CD13 may regulate endocytosis in the context of infection or injury, we investigated the effect of inflammatory signals on CD13 itself. Previous studies had suggested that CD13 expression levels were increased in human peripheral blood monocytes in response to injury in vivo or LPS treatment in vitro (27). In agreement with this finding, we found that LPS stimulation of WT macrophages induced CD13 protein expression over 4-fold in a time-dependent manner (Fig.…”

Monitoring peri-operative immune suppression in renal cancer patients

“…In an earlier study of polytrauma patients the observed decrease in monocytic HLA-DR expression was accompanied by a delayed strong increase of membrane peptidase APN/ CD13 expression (23). In the present study, we describe for the first time that the decrease in monocytic HLA-DR intensity is paralleled by an increase in APN/CD13 intensity in advanced RCC tumor stages.…”

Platelet-derived growth factor-BB has neurorestorative effects and modulates the pericyte response in a partial 6-hydroxydopamine lesion mouse model of Parkinson's disease

“…Consistently, we also observed a significant increase in CD13 expression in 6-OHDA-lesioned animals that was reversed by PDGF-BB. CD13 levels are known to increase upon angiogenesis and inflammation (Di Matteo et al, 2011;Huschak et al, 2003). PDGF-BB may reduce the inflammation in the striatum and CD13 expression.…”