last updated April 2013
New insight on leukocyte recruitment
A new signaling pathway mediates key step in inflammation
A team of researchers based in
The inflammatory response unleashes a cascade of cellular events. A key step is the recruitment of white blood cells armed to combat the inflammatory threat. Recruitment is a complex process, requiring the leukocytes to adhere to the interior surface of blood vessels (endothelium), and from there migrate through the blood vessels to the site of inflammation. A class of cell membrane-spanning proteins known as integrins is the major player in this process of adhesion.
The researchers, led by Jian-Guo Geng at the Shanghai Institutes for Biological Sciences, have described a signaling pathway that appears to regulate the activation of integrin-mediated adhesion1.
Initially the study showed that mice lacking P-selectin, a protein found in the endothelium, had impaired leukocyte adhesion. Selectins act to bring leukocytes into proximity with integrins, and when soluble P-selectin was made available to the P-selectin deficient mice, the adhesion function was ‘rescued’.
Further investigation revealed that P-selectin binds to P-selectin glycoprotein ligand 1 (PGSL-1), triggering a signaling cascade in the leukocytes, and ultimately activating the integrins.