Studies on the Molecular Basis of CD44 and Hyaluronan in Neutrophils Activation

• Main Authors: Chia-Hui Lin, 林佳慧
• Other Authors: 余家利
• Format: Others
• Language: en_US
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/89829382875171383664

碩士 === 國立臺灣大學 === 分子醫學研究所 === 101 === CD44 is a multifunctional cell-surface glycoprotein that is involved in cell-cell interaction, cell adhesion, migration, proliferation and angiogenesis and is widely expressed in a large number of mammalian cell types. Hyaluronic acid (HA), one of important ligand of CD44, is distributed widely throughout connective, epithelial, and neural tissues. After CD44-HA binding initiates CD44 downstream signaling pathways, the signaling induces multiple functions. Previous studies have demonstrated that CD44 induces the lymphocyte activation, recirculation, and homing. Some paper have shown that CD44-HA interaction could regulate inflammation, tissue injury and repair through regulating inflammatory cell recruitment, release of inflammatory cytokines, and stem cell migration. However, the effects of CD44-HA interaction on neutrophils remained unclear. In our preliminary study, several interesting results were found. First, we found that the LPS and anti-CD44 could increase the expression of CD44 on PMN. HA could also enhance the phagocytosis activity and cytoskeleton rearrangement of PMN and its binding to CD44 could induce the interlukin-8 (IL-8) production. Furthermore, we found that HA could induce phosphorylation of MAP kinase (p38), and ERK1/2 signaling pathways. In the future, we will test the effect of different pro-inflammatory cytokines on the surface expression of CD44 on PMN. The signaling pathways will be selectively blocked for the observation of their effects on phagocytosis and cytokines production of PMN. In addition, the hyaluronidase will be used to evaluate the CD44-HA interaction on PMN. Lastly, the knockdown of CD44 expression in PMN will be carried out to define the CD44-independent mechanisms by which HA can mediate inflammation.