Cell Adhesion

Carbohydrate Remodeling

Science's STKE  30 Sep 2003:
Vol. 2003, Issue 202, pp. tw384-TW384
DOI: 10.1126/stke.2003.202.tw384

CD44 is an adhesion molecule that is the receptor for hyaluron. Although most cell types express CD44, very few bind hyaluron, which suggests that binding activity is a regulated process. Lipopolysaccharide (LPS) and cytokines stimulate hyaluron-mediated cell adhesion by stimulating CD44's binding activity. Gee et al. investigated the mitogen-activated protein (MAPK) cascades in the LPS-stimulated increase in CD44 binding. Using pharmacologic inhibitors of either p38 MAPK or ERK1 and 2 (ERK1/2) signaling, the authors found out that in interleukin-10 (IL-10) refractory THP-1 cells, a monocytic cell line, LPS activated an ERK1/2 cascade, which led to the production of the cytokine TNF-α (tumor necrosis factor α). TNF-α then stimulated a sialidase activity in the cytosol in a pathway involving p38 MAPK. The role for regulated glycosylation was confirmed by treating cells (monocytes or THP-1 cells) with sialidase, which promoted CD44-mediated hyaluron cell attachment. Furthermore, treatment of the cells with a sialidase inhibitor before LPS or TNF-α stimulation blocked cell adherence. Thus, sequential activation of the ERK then p38 MAPK pathways regulates CD44-mediated cell adhesion by stimulating enzymes involved in receptor carbohydrate remodeling.

K. Gee, M. Kozlowski, A. Kumar, Tumor necrosis factor-α induces functionally active hyaluronan-adhesive CD44 by activating sialidase through p38 mitogen-activated protein kinase in lipopolysaccharide-stimulated human monocytic cells. J. Biol. Chem. 278, 37275-37287 (2003). [Abstract] [Full Text]