166 Granzyme K stimulates a novel pathway of complement activation
نویسندگان
چکیده
Granzyme K (gzmK) expressing CD8+ T-cells have recently been described as a novel effector T-cell population found in variety of inflamed tissues including rheumatoid arthritis synovium, lupus nephritis, and inflammatory bowel disease colon. GzmK also identified major cutaneous lupus, psoriatic skin synovium. However, the overall function gzmK has relatively undefined. Prior studies shown gzmK+ CD8 low cytotoxic capability but potential to drive inflammation. Here, we show that acts mechanism complement activation. cleaves C2 C2a C4 C4b form an active C3 convertase into bioactive C3a C3b. incubated with purified components C2, C3, results C3b opsonization on surface endothelial cells well mast cell degranulation through production C3a. Further, incubation C4, C5, C6, C7, C8, C9 forms complete membrane attack complex (MAC), final common pathway These effects are specific granzyme A (gzmA), other tryptase activity, do not result or MAC formation. Like granzymes, is heavily positively charged molecule can bind negative molecules cells. Interference binding addition negatively heparin limits subsequent suggesting must be bound convertase. Taken together, define new activation independent previously well-described classical, alternative, mannose-binding lectin pathways dependent inflammation states.
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ژورنال
عنوان ژورنال: Journal of Investigative Dermatology
سال: 2023
ISSN: ['1523-1747', '0022-202X']
DOI: https://doi.org/10.1016/j.jid.2023.03.167