Galectin-3 aggravates experimental polymicrobial sepsis by impairing neutrophil recruitment to the infectious focus
| Autor: | Paulo Henrique Melo, Alexandre Kanashiro, Vanessa F. Borges, Lilian Cataldi Rodrigues, José C. Alves-Filho, Sean R. Stowell, Marcelo Dias-Baruffi, Richard D. Cummings, Aline Gozzi, Marcos C. Borges, Daniele C. Nascimento, Fernando Silva Ramalho, Douglas Silva Prado, Fernando Q. Cunha, Raphael Gomes Ferreira |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Microbiology (medical) Galectin 3 Galectins INFLAMAÇÃO Endogeny Systemic inflammation Sepsis Mice 03 medical and health sciences Peritoneal cavity 0302 clinical medicine medicine Animals Humans Lung Aged Mice Knockout Coinfection Septic shock business.industry Organ dysfunction Blood Proteins Middle Aged medicine.disease Mice Inbred C57BL Disease Models Animal 030104 developmental biology Infectious Diseases medicine.anatomical_structure Neutrophil Infiltration Galectin-3 Immunology Female Peritoneum medicine.symptom business Infiltration (medical) 030215 immunology |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 0163-4453 |
| Popis: | Sepsis is an overwhelming systemic inflammation resulting from an uncontrolled infection that causes extensive tissue damage, organ dysfunction and eventually death. A growing body of evidence indicates that impaired neutrophil migration to the site of infection is associated with poor outcome in sepsis. Here we show that galectin-3 (Gal-3), an endogenous glycan-binding protein, plays a critical role in sepsis outcome. We found that serum Gal-3 concentration increased in patients with septic shock and mice undergoing sepsis induced by cecal ligation and puncture (CLP). Mice deficient in Gal-3 (Gal-3 KO) are more resistant to sepsis induced by CLP, showing lower levels of biochemical markers and neutrophil infiltration for organ injury/dysfunction than those observed in wild-type mice (WT). Furthermore, Gal-3 KO mice show an increased number of neutrophils in the primary focus of infection and reduced bacterial loads in the peritoneal cavity, blood, and lungs. Mechanistically, blood neutrophils from septic mice show higher levels of surface-bound Gal-3 than neutrophils from naive mice. The deficiency of Gal-3 was associated with increased rolling and adhesion of these cells in mesenteric venules. Our results indicate that Gal-3, secreted during sepsis, inhibits neutrophil migration into the infectious focus, which promotes the bacterial spread and worsens the outcome of sepsis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect