α1-Acid glycoprotein decreases neutrophil migration and increases susceptibility to sepsis in diabetic mice.
Diabetes
; 61(6): 1584-91, 2012 Jun.
Article
en En
| MEDLINE
| ID: mdl-22415874
ABSTRACT
The mechanisms underlying immune deficiency in diabetes are largely unknown. In the present study, we demonstrate that diabetic mice are highly susceptible to polymicrobial sepsis due to reduction in rolling, adhesion, and migration of leukocytes to the focus of infection. In addition, after sepsis induction, CXCR2 was strongly downregulated in neutrophils from diabetic mice compared with nondiabetic mice. Furthermore, CXCR2 downregulation was associated with increased G-protein-coupled receptor kinase 2 (GRK2) expression in these cells. Different from nondiabetic mice, diabetic animals submitted to mild sepsis displayed a significant augment in α1-acid glycoprotein (AGP) hepatic mRNA expression and serum protein levels. Administration of AGP in nondiabetic mice subjected to mild sepsis inhibited the neutrophil migration to the focus of infection, as well as induced l-selectin shedding and rise in CD11b of blood neutrophils. Insulin treatment of diabetic mice reduced mortality rate, prevented the failure of neutrophil migration, impaired GRK2-mediated CXCR2 downregulation, and decreased the generation of AGP. Finally, administration of AGP abolished the effect of insulin treatment in diabetic mice. Together, these data suggest that AGP may be involved in reduction of neutrophil migration and increased susceptibility to sepsis in diabetic mice.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Orosomucoide
/
Movimiento Celular
/
Sepsis
/
Infiltración Neutrófila
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Diabetes Mellitus Experimental
/
Neutrófilos
Límite:
Animals
Idioma:
En
Revista:
Diabetes
Año:
2012
Tipo del documento:
Article
País de afiliación:
Brasil