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Updated: Jun 24, 2026

Modified Yeast-Two-Hybrid System to Identify Proteins Interacting with the Growth Factor Progranulin
Published on: January 17, 2012
Progranulin enhances complement component 5a-primed neutrophil activation in antineutrophil cytoplasmic
Yuan-Yuan Lu1, Xing-Yu Chen2, Tie-Gang Lv3
1Department of Medicine, Division of Nephrology. The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, 010050, China; Department of Medicine, Division of Respiratory and Critical Care Medicine, Affiliated Hospital of Chifeng University, Chifeng, Inner Mongolia Autonomous Region, 024000, China.
Background:
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disorder characterized by vascular inflammation and the activation of neutrophils. Complement component 5a (C5a) is pivotal in neutrophil priming and ANCA-mediated activation. Although progranulin (PGRN) is recognized for its involvement in inflammatory processes, yet its specific role in ANCA-associated vasculitis (AAV) remains poorly understood This study investigates the functional interplay between PGRN and C5a in enhancing neutrophil activation in response to ANCA stimulation.
Methods:
Neutrophils were primed with recombinant PGRN and subsequently stimulated with myeloperoxidase (MPO)-ANCA or proteinase 3 (PR3)-ANCA-positive immunoglobulin G. The respiratory burst was evaluated through dihydrorhodamine oxidation, while degranulation was quantified by measuring lactoferrin release. Additionally, the effects of PGRN-neutralizing antibodies on C5a-primed neutrophils were evaluated.
Results:
PGRN significantly upregulated membrane-bound proteinase 3 expression in neutrophils compared to untreated controls (368.0 ± 18.5 vs. 178.0 ± 14.7, p < 0.001) and enhanced MPO release in the culture supernatants (1462.8 ± 202.2 vs. 526.8 ± 118.8, p < 0.001). PGRN-primed neutrophils demonstrated increased respiratory burst activity (p < 0.001) and elevated lactoferrin release (p < 0.001) compared to non-primed cells. Inhibition of PGRN significantly diminished ANCA-mediated oxygen radical production (p < 0.001) and degranulation (p < 0.001) in C5a-primed neutrophils.
Conclusions:
PGRN functionally enhances C5a-mediated neutrophil activation, suggesting a cooperative effect but not a direct molecular interaction. This in vitro study using human neutrophils explores the cooperative effects of PGRN and C5a in ANCA-induced activation. Future research should investigate the use of PGRN inhibitors to mitigate inflammation in AAV.
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