Researchers led by Dr. Claudine S. Bonder of the University of Adelaide, Adelaide, South Australia, Australia implicate sphingosine kinase-1 in neutrophil recruitment to sites of inflammation. They report their data in the July 2010 issue of The American Journal of Pathology.
Neutrophils, which make up nearly 70% of white blood cell in the blood stream, are first-responder immune cells that migrate to sites of infection and inflammation, where they secrete inflammatory molecules and fight pathogens. These and other white blood cells are targeted to sites of inflammation and infection via adhesive molecules, such as integrins, that are upregulated on the surface of blood vessels.
To determine if sphingosine kinase-1, an enzyme that both cleaves and generates important signaling molecules within cells, contributes to integrin-mediated neutrophil recruitment, Sun et al examined inflammatory responses in a model of human blood vessels. Sphingosine kinase-1 was required for integrin activation and subsequent neutrophin adhesion in this system. Taken together, these data support sphingosine kinase-1 as a broad-spectrum target for inhibiting neutrophil recruitment and subsequent inflammatory and immune disorders.
Dr. Bonder and colleagues "suggest that [sphingosine kinase-1 may be the single target required for an effective broad spectrum therapeutic target to combat inflammatory and immune disorders."
- Sun WY, Pitson SM, Bonder CS. Tumor necrosis factor-induced neutorphil adhesion occurs via sphingosine kinase-1-dependent actuaion of endothelial integrin. Am J Pathol, 2010, 177: 436-446
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