Help on the Way

01.10.2007

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In infection, the body calls out the "paramedics" – the white blood cells, or leukocytes – to come to the rescue. Chemical substances called chemokines put through the emergency call and direct leukocytes to the right location.
 
Leukocytes maneuver their way through the body's transport system – the blood vessels – but they must be able to exit at the site of the infection. The chemokines help out by activating molecules on the leukocyte surface called integrins – sticky proteins that act as brakes on the circulating cells and guide them out of the blood vessels.
 
Prof. Ronen Alon of the Immunology Department has now discovered some previously unidentified links in this process. One of these is a biochemical switch that acts on the integrins, stabilizing them in a configuration that enhances their adhesiveness. Another is the mechanical force created by the blood flowing against the vessel wall, otherwise known as shear force. Alon, postdoctoral researcher Dr. Eilon Woolf and colleagues discovered that shear force, which, intuitively, should disrupt cell adhesion, is in fact crucial to initiating the series of events in which the sticky integrin molecules bring the leukocytes to a halt and facilitate their exit from the blood vessels. In research published recently in Nature Immunology, the team showed that if either of these links is missing, the leukocytes can't make their way from the blood to the scene of the infection.
 
Several years ago, a rare disease caused by a defective gene for leukocyte adhesion, called LAD-III, was identified by Dr. Sara Feigelson and Ronit Pasvolsky of Alon's lab, in collaboration with Prof. Amos Etzioni, Head of the Pediatrics Department of the Meyer Children's Hospital in Haifa. This severe immunodeficiency syndrome is associated with a higher than usual white blood cell count in the blood and severe bleeding disorders. Alon's team, together with colleagues in the Molecular Genetics Department and Biological Services unit recently conducted a genetic analysis on samples from LAD-III patients, and their research revealed that one single protein is faulty in this disease. This protein, found in many cell types, determines the biochemical switch that's turned on by the chemokines to activate integrin adhesiveness on all white blood cells – substantiating the team's earlier findings on the importance of each link in the chain of events that directs the white blood cells out of the blood vessels to the sites of infection.
 
Prof. Ronen Alon's research is supported by the Belle S. and Irving E. Meller Center for the Biology of Aging. Prof. Alon is the incumbent of the Linda Jacobs Chair in Immune and Stem Cell Research.

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