Drawing a crowd: Understanding the signals that bring inflammatory cells into the lung

Understanding the connection between influx of immune cells into the lung and acute lung injury is essential, since lung damage tends to occur secondary to increased lung inflammation. In a study appearing online on February 16 in advance of print publication in the March issue of the Journal of Clinical Investigation, Klaus Ley and colleagues from the University of Virginia in Charlottesville demonstrate that expression of an immune molecule called CXCR2 on blood vessel wall cells (as opposed to immune cells themselves) mediates the influx of white blood cells, called neutrophils, into the lung during acute bacterial infection. The researchers stimulated neutrophil influx to the lungs of mice by having the mice breathe in a bacterial sugar called lipopolysaccharide (LPS).

As expected, mice that were genetically modified so that they did not express CXCR2 (called CXCR2 knockout mice) failed to recruit neutrophils. However, the authors were surprised to find that normal mice whose normal bone marrow cells (ie., immune cells) were replaced with cells from the CXCR2 knockout mice were able to recruit neutrophils to the lung at a rate of about 50% of normal, suggesting that even though the knockout neutrophils did not have CXCR2, they were still able to migrate to the lung. Using a specific antibody that detects CXCR2 protein, the researchers found that CXCR2 is present on blood vessel wall cells of the lung and in cells called epithelial cells that line the airways.

The authors report that it is this pattern of CXCR2 expression on lung cells, and not the presence of CXCR2 on the neutrophils themselves, which is essential for neutrophil recruitment in response to LPS and the resulting acute lung injury.

TITLE: Critical role of endothelial CXCR2 in LPS-induced neutrophil migration into the lung

Klaus Ley
University of Virginia, Charlottesville, Virginia, USA
Phone: (434) 243-9966; Fax: (434) 92

Contact: Brooke Grindlinger
Journal of Clinical Investigation

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