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Endothelial expression of selectins during endotoxin preconditioning
P Bauer1, T Welbourne, T Shigematsu
1Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130-3932, USA.
Summary
Bacterial endotoxins (lipopolysaccharide, LPS) can protect tissues from inflammation. This study found LPS-preconditioning reduces E- and P-selectin expression, suggesting lymphocytes, not nitric oxide or superoxide, mediate this protective effect.
Area of Science:
- Immunology
- Vascular Biology
- Cellular Biology
Background:
- Bacterial endotoxins, specifically lipopolysaccharide (LPS), are known to induce a state of tissue resistance against subsequent inflammatory challenges, a phenomenon termed LPS-preconditioning (LPS-PC).
- The precise molecular and cellular mechanisms governing this LPS-PC-mediated protective response are not fully elucidated.
- Understanding these mechanisms is crucial for developing therapeutic strategies against inflammatory diseases.
Purpose of the Study:
- To investigate whether LPS-preconditioning alters the protein expression of E-selectin and P-selectin in response to a subsequent LPS challenge.
- To explore the roles of nitric oxide (NO), superoxide, and lymphocytes in mediating the LPS-PC-induced modulation of selectin expression.
Main Methods:
- Utilized a dual-radiolabeled monoclonal antibody technique to quantify E- and P-selectin protein upregulation in mouse models.
- Employed wild-type (C57BL/6J) mice, genetically modified mice deficient in nitric oxide synthase isoforms or overexpressing superoxide dismutase, and severe combined immunodeficient (SCID) mice.
Main Results:
- LPS-preconditioning significantly reduced E-selectin (66%) and P-selectin (33%) expression in the gut of wild-type mice.
- Similar reductions in E-selectin expression were observed in mice lacking endothelial or inducible nitric oxide synthase, or overexpressing Cu/Zn superoxide dismutase.
- Severe combined immunodeficient mice, lacking lymphocytes, showed only partial inhibition of the LPS-PC response, indicating a potential role for circulating lymphocytes.
Conclusions:
- LPS-preconditioning demonstrably reduces E- and P-selectin expression in specific vascular beds, such as the gut.
- The blunted selectin response during LPS-PC is not primarily mediated by nitric oxide or superoxide pathways.
- Circulating lymphocytes appear to play a contributing role in the LPS-preconditioning phenomenon.