Recombinant Human Plasma Gelsolin Stimulates Phagocytosis while Diminishing Excessive Inflammatory Responses in Mice with Pseudomonas aeruginosa Sepsis

International Journal of Molecular Sciences

Andrzej Namiot¹  Katarzyna Niemirowicz-Laskowska²  Piotr Deptuła²  Robert Bucki²  SuhanyaV. Prasad²  Urszula Wnorowska²  Ewelina Piktel²  Mateusz Cieśluk²  Grzegorz Król³  Bonita Durnaś³  Joanna Reszeć⁴  PaulA. Janmey⁵  AgnieszkaZ. Wilczewska⁶  KarolinaH. Markiewicz⁶ 

[1] Department of Anatomy, Medical University of Bialystok, Mickiewicza 2b, 15-222 Bialystok, Poland;Department of Medical Microbiology and Nanobiomedical Engineering, Medical University of Bialystok, Mickiewicza 2c, 15-222 Bialystok, Poland;Department of Microbiology and Immunology, the Faculty of Medicine and Health Sciences of the Jan Kochanowski University in Kielce, Stefana Żeromskiego 5, 25-001 Kielce, Poland;Department of Pathology, Medical University of Bialystok, Waszyngtona 13, 15-269 Bialystok, Poland;Institute for Medicine and Engineering, University of Pennsylvania, 3340 Smith Walk, Philadelphia, PA 19104, USA;Institute of Chemistry, University of Białystok, Ciołkowskiego 1K, 15-245 Bialystok, Poland;

关键词: plasma gelsolin;    inflammation;    phagocytosis;    sepsis;    Pseudomonas aeruginosa;   

DOI  :  10.3390/ijms21072551

来源: DOAJ

【 摘 要 】

Plasma gelsolin (pGSN) is a highly conserved abundant circulating protein, characterized by diverse immunomodulatory activities including macrophage activation and the ability to neutralize pro-inflammatory molecules produced by the host and pathogen. Using a murine model of Gram-negative sepsis initiated by the peritoneal instillation of Pseudomonas aeruginosa Xen 5, we observed a decrease in the tissue uptake of IRDye^®800CW 2-deoxyglucose, an indicator of inflammation, and a decrease in bacterial growth from ascitic fluid in mice treated with intravenous recombinant human plasma gelsolin (pGSN) compared to the control vehicle. Pretreatment of the murine macrophage line RAW264.7 with pGSN, followed by addition of Pseudomonas aeruginosa Xen 5, resulted in a dose-dependent increase in the proportion of macrophages with internalized bacteria. This increased uptake was less pronounced when cells were pretreated with pGSN and then centrifuged to remove unbound pGSN before addition of bacteria to macrophages. These observations suggest that recombinant plasma gelsolin can modulate the inflammatory response while at the same time augmenting host antibacterial activity.

【 授权许可】

Unknown