L-selectin-deficient mice have impaired leukocyte recruitment into inflammatory sites

doi:10.1084/jem.181.6.2259

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L-selectin-deficient mice have impaired leukocyte recruitment into inflammatory sites

TF Tedder, DA Steeber and P Pizcueta
Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA.

L-selectin, a cell surface adhesion molecule that is expressed by most leukocytes, mediates leukocyte rolling along vascular endothelium at sites of inflammation. The contribution of L-selectin to leukocyte migration in models of chronic inflammation was assessed by using mice that lack cell surface L-selectin expression. Significant inhibition of neutrophil (56-62%), lymphocyte (70-75%), and monocyte (72-78%) migration into an inflamed peritoneum was observed 24 and 48 h after administration of thioglycollate, an inflammatory stimulus. L-selectin- deficient mice were also significantly impaired in delayed-type hypersensitivity reactions. Footpad swelling in response to sheep red blood cell challenge was reduced 75% in L-selectin-deficient mice compared with wild-type mice. Ear swelling in a model of contact hypersensitivity induced by oxazolone challenge was also reduced by 69% compared to wild-type mice. Consistent with L-selectin-mediating leukocyte migration into diverse vascular beds during inflammation, L- selectin-deficient mice were significantly resistant to death resulting from lipopolysaccharide (LPS)-induced toxic shock. LPS administration resulted in a 90% mortality rate in control mice after 24 h, while there was a 90% survival rate in L-selectin-deficient mice. These results demonstrate that L-selectin plays a prominent role in leukocyte homing to nonlymphoid tissues during inflammation and that blocking this process can be beneficial during pathological inflammatory responses.
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JILMA, B., BLANN, A., PERNERSTORFER, T., STOHLAWETZ, P., EICHLER, H.-G., VONDROVEC, B., AMIRAL, J., RICHTER, V., WAGNER, O.�F. (1999). Regulation of Adhesion Molecules during Human Endotoxemia . No Acute Effects of Aspirin. Am. J. Respir. Crit. Care Med. 159: 857-863 [Abstract] [Full Text]
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