L-selectin-deficient mice have impaired leukocyte recruitment into inflammatory sites.
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.
Tedder
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Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Steeber
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Pizcueta
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D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000502:physiology*; D003433:Crosses, Genetic; D003877:Dermatitis, Contact / Q000276:immunology* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000502:physiology / Q000503:physiopathology; D007249:Inflammation / Q000276:immunology* / Q000503:physiopathology; D019041:L-Selectin; D007962:Leukocytes / Q000276:immunology / Q000502:physiology*; D008214:Lymphocytes / Q000276:immunology / Q000502:physiology; D008264:Macrophages / Q000276:immunology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009504:Neutrophils / Q000276:immunology / Q000502:physiology; D010081:Oxazolone
D015815:Cell Adhesion Molecules; D019041:L-Selectin; D010081:Oxazolone