Project Details
Projekt
The impact of polysialic acid on the innate immune system of the female and male reproductive tract
Applicant
Privatdozent Dr. Sebastian P. Galuska
Subject Area
Reproductive Medicine, Urology
Term
from 2011 to 2017
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 200367144
In mammals sialic acids are mostly present as terminal monomers of glycans. However, also sialic acid polymers are present on glycoproteins, which can be synthesized by the polysialyltransferases ST8SiaII and ST8SiaIV. In the neuronal system polysialic acid (polySia) plays - as a posttranslational modification of the neural cell adhesion molecule NCAM - a crucial role in the regulation of cell-cell interaction mediating many essential processes. In addition polySia regulates via a direct interaction with e.g. growth factors, MARCKS (myristoylated alanin-rich C kinase substrate) and histone 1 the differentiation of neuronal cells. Furthermore, in the respiratory system polySia is discussed to counteract, due to its histone-binding abilities, the cytotoxicity of extracellular histones of NET (neutrophil extracellular traps), which are formed during inflammation. We suggest that the female and the male reproductive tract represent two further biological systems where polySia chains may influence the innate immune system. We have already identified two antimicrobial factors (lactotransferrin und beta-defensin 4) as binding partners of polySia-chains in human semen. Our working hypothesis is that at sites of inflammation the interaction of polySia with histones of NET leads to an inhibition of the cytotoxicity of extracellular histones and additionally to an accumulation of antimicrobial factors like lactotransferrin und beta-defensin 4. In parallel increasing concentrations of polySia may inhibit via a MARCKS-polySia interaction the activation of further neutrophils (polySia as feedback inhibitor). These processes may play a role in the female reproductive tract after insemination as well as during an inflammation of the epididymis. The described issues will be studied using a combination of in vitro experiments and in vivo models.
DFG Programme
Research Grants
