CELL ADHESION Carbohydrate Remodeling

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- (tumor necrosis factor ). TNF- 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- 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- 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]

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VIRTUAL JOURNAL
Tumor Necrosis Factor- Induces Functionally Active Hyaluronan-adhesive CD44 by Activating Sialidase through p38 Mitogen-activated Protein Kinase in Lipopolysaccharide-stimulated Human Monocytic Cells

Katrina Gee, Maya Kozlowski, and Ashok Kumar (26 September 2003)
J. Biol. Chem. 278 (39), 37275. [DOI: 10.1074/jbc.M302309200]
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