Journal of inflammation research · 2026
Transforming Growth Factor-β1 Drives Neutrophil Chemokinesis, Not Chemotaxis.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
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Crowley Louise E, Jenkins Ellen, McGee Kirsty C, Smith Theodore S, Hazeldine Jon, Stockley Robert A, Thickett David R, Parekh Dhruv, Scott Aaron
Аннотация
PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a devastating condition that is characterized by dysregulated repair responses to alveolar epithelial damage and progressive remodeling of the lung interstitium. Neutrophils are critical responders to tissue injury, but their role in organ fibrosis pathogenesis remains unclear. Neutrophil numbers are increased in bronchoalveolar spaces of IPF patients, and neutrophil activation markers are elevated in fibrotic lung tissue. However, the key mediators driving neutrophil movement in fibrotic lung diseases are unknown. Transforming growth factor-beta 1 (TGFβ1) is a critical pro-fibrotic cytokine, but its effect on neutrophil movement remains unclear. This mechanistic, exploratory study aimed to determine whether TGFβ1 alters neutrophil migration in a direction-dependent (chemotaxis) or direction-independent (chemokinesis) manner and to assess whether TGFβ1 exposure is accompanied by functional changes consistent with neutrophil priming.
METHODS: This study utilized human neutrophils from healthy donors to model aspects of a TGFβ1-rich environment. Neutrophil movement was assessed using a transwell migration assay and by real-time tracking of human neutrophils within an Insall chamber. Extracellular release of superoxide anions and nucleic acid were assessed by lucigenin-amplified chemiluminescence, and fluorometry, respectively. Expression of cell surface markers, TGFβ receptor 1 and pSmad2/3 were assessed using flow cytometry and Western blot.
RESULTS: This study revealed that TGFβ1 drives neutrophil chemokinesis, but not chemotaxis, and that pre-treatment with TGFβ1 amplified selected movement responses to the established chemoattractants, interleukin-8 and N-Formylmethionine-leucyl-phenylalanine. TGFβ1 also increased total superoxide anion production and nucleic acid release, but did not alter cell surface expression of adhesion (CD11b and CD62L) or degranulation (CD66b) markers.
CONCLUSION: Together, these data suggest that TGFβ1 promotes neutrophil chemokinesis, rather than chemotaxis, and that this may reflect transition into a priming-like state with potential relevance to neutrophil behavior in conditions such as fibrotic lung disease.
METHODS: This study utilized human neutrophils from healthy donors to model aspects of a TGFβ1-rich environment. Neutrophil movement was assessed using a transwell migration assay and by real-time tracking of human neutrophils within an Insall chamber. Extracellular release of superoxide anions and nucleic acid were assessed by lucigenin-amplified chemiluminescence, and fluorometry, respectively. Expression of cell surface markers, TGFβ receptor 1 and pSmad2/3 were assessed using flow cytometry and Western blot.
RESULTS: This study revealed that TGFβ1 drives neutrophil chemokinesis, but not chemotaxis, and that pre-treatment with TGFβ1 amplified selected movement responses to the established chemoattractants, interleukin-8 and N-Formylmethionine-leucyl-phenylalanine. TGFβ1 also increased total superoxide anion production and nucleic acid release, but did not alter cell surface expression of adhesion (CD11b and CD62L) or degranulation (CD66b) markers.
CONCLUSION: Together, these data suggest that TGFβ1 promotes neutrophil chemokinesis, rather than chemotaxis, and that this may reflect transition into a priming-like state with potential relevance to neutrophil behavior in conditions such as fibrotic lung disease.