Các kích thích khác nhau kích hoạt các con đường bẫy ngoại bào của bạch cầu trung tính

eLife - Tập 6
Elaine F. Kenny1, Alf Herzig1, Renate Krüger2,3, Aaron Muth4, Santanu Mondal4, Paul R. Thompson4, Volker Brinkmann5, Horst von Bernuth6,2,7,3, Arturo Zychlinsky1
1Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Berlin, Germany
2Department of Paediatric Pneumology and Immunology, Outpatient Clinic for Primary Immunodeficiencies, Charité Medical School, Berlin, Germany
3Sozialpädiatrisches Zentrum, Charité Medical School, Berlin, Germany
4Department of Biochemistry and Pharmacology, University of Massachusetts Medical School, Worcester, United States;
5Microscopy Core Facility, Max Planck Institute for Infection Biology, Berlin, Germany
6Berlin Centre for Regenerative Therapies, Charité Medical School, Berlin, Germany
7Labor Berlin, Section for Immunology, Charité–Vivantes GmbH, Berlin, Germany

Tóm tắt

Bạch cầu trung tính giải phóng các bẫy ngoại bào (NETs) mà bắt giữ các tác nhân gây bệnh và có chức năng gây bệnh trong nhiều bệnh lý khác nhau. Chúng tôi đã nghiên cứu các con đường NETosis được kích thích bởi năm tác nhân; PMA, ionophore canxi A23187, nigericin, Candida albicans và Group B Streptococcus. Chúng tôi đã nghiên cứu sự sản xuất NET trong các bạch cầu trung tính từ những người hiến tặng khỏe mạnh với các chất ức chế các phân tử thiết yếu cho NETs do PMA kích thích, bao gồm protein kinase C, canxi, các gốc tự do oxy, các enzyme myeloperoxidase (MPO) và elastase bạch cầu trung tính. Thêm vào đó, các bạch cầu trung tính từ bệnh nhân mắc bệnh hạt mãn tính, có sự đột biến trong phức hợp NADPH oxidase hoặc một bệnh nhân thiếu MPO cũng đã được xem xét. Chúng tôi cho thấy rằng PMA, C. albicans và GBS sử dụng một con đường liên quan để kích thích NET, trong khi các ionophore yêu cầu một con đường thay thế nhưng các NET được sản xuất bởi tất cả các tác nhân kích thích đều có hoạt tính proteolitic, tiêu diệt vi khuẩn và chủ yếu được cấu tạo từ DNA nhiễm sắc thể. Do đó, chúng tôi chứng minh rằng NETosis diễn ra thông qua nhiều cơ chế tín hiệu, gợi ý rằng sự loại bỏ của NETs là quan trọng trong phòng thủ của chủ thể.

Từ khóa


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