P-selectin glycoprotein ligand-1 regulates adhesive properties of the endothelium and leukocyte trafficking into adipose tissue
| Autor: | Hana M, Russo, Kevin J, Wickenheiser, Wei, Luo, Miina K, Ohman, Luigi, Franchi, Andrew P, Wright, Peter F, Bodary, Gabriel, Núñez, Núñez, Gabriel, Daniel T, Eitzman |
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| Rok vydání: | 2010 |
| Předmět: |
Male
medicine.medical_specialty Endothelium Physiology Adipose tissue Inflammation Article Mice Internal medicine Genetic model E-selectin medicine Cell Adhesion Leukocytes Animals Obesity Chemokine CCL2 Crosses Genetic Bone Marrow Transplantation Mice Knockout Leptin receptor Membrane Glycoproteins integumentary system biology Reverse Transcriptase Polymerase Chain Reaction Monocyte Receptors Interleukin-1 Animal Feed P-Selectin Endocrinology medicine.anatomical_structure Adipose Tissue biology.protein Receptors Leptin P-selectin glycoprotein ligand-1 Female medicine.symptom Cardiology and Cardiovascular Medicine E-Selectin |
| Zdroj: | Circulation research. 107(3) |
| ISSN: | 1524-4571 |
| Popis: | Rationale : Adhesive interactions between endothelial cells and leukocytes affect leukocyte trafficking in adipose tissue. The role of P-selectin glycoprotein ligand-1 (Psgl-1) in this process is unclear. Objective : The goal of this study was to determine the effect of Psgl-1 deficiency on adhesive properties of the endothelium and on leukocyte recruitment into obese adipose depots. Methods and Results : A genetic model of obesity was generated to study the effects of Psgl-1 deficiency on leukocyte trafficking. Leukocyte-endothelial interactions were increased in obese leptin receptor mutant mice ( Lepr db/db ,Psgl-1 +/+ ) but not obese Psgl-1–deficient mice ( Lepr db/db ,Psgl-1 −/− ), when compared with lean mice ( Lepr +/+ ,Psgl-1 +/+ ). This effect of Psgl-1 deficiency was due to indirect effects of Psgl-1, because Psgl-1 +/+ adoptively transferred leukocytes did not exhibit enhanced rolling in Lepr db/db ,Psgl-1 −/− mice. Additionally, circulating levels of P-selectin, E-selectin, monocyte chemoattractant protein-1, and macrophage content of visceral adipose tissue were reduced in Lepr db/db ,Psgl-1 −/− compared with Lepr db/db ,Psgl-1 +/+ mice. Reduced leukocyte-endothelial interactions and macrophage content of visceral adipose tissue due to Psgl-1 deficiency was also observed in a diet-induced obese mouse model. Psgl-1 −/− mice were resistant to the endothelial effects of exogenous IL-1β, suggesting that defective cytokine signaling contributes to the effect of Psgl-1 deficiency on leukocyte-endothelial interactions. Mice deficient in the IL-1 receptor also had reduced levels of circulating P-selectin, similar to those observed in Psgl-1 −/− mice. Conclusions : Deficiency of Psgl-1 is associated with reduced IL-1 receptor-mediated adhesive properties of the endothelium and is protective against visceral fat inflammation in obese mice. |
| Databáze: | OpenAIRE |
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