Lundgren Sigrid, Petruk Ganna, Wallblom Karl, Cardoso José F P, Strömdahl Ann-Charlotte, Forsberg Fredrik, Luo Congyu, Nilson Bo, Hartman Erik, Fisher Jane, Puthia Manoj, Saleh Karim, Schmidtchen Artur
Division of Dermatology and Venereology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
Department of Dermatology, Skåne University Hospital, Lund, Sweden.
Front Med (Lausanne). 2025 Jul 21;12:1609347. doi: 10.3389/fmed.2025.1609347. eCollection 2025.
Inflammation is integral to wound healing; yet, its dynamics in normally healing epidermal wounds are not fully characterized. To this end, we analyzed longitudinal wound fluid samples collected from epidermal suction blister wounds in healthy volunteers.
A total of 48 control wounds were induced by suction blister method in 24 healthy volunteers-1 on each thigh. Immunoassay, MALDI-TOF mass spectrometry, and microbiological methods were applied to analyze cytokine dynamics, neutrophil activity, and bacterial colonization and levels in wound swabs and dressings during epidermal wound healing, focusing on viable cultivable wound bacteria.
Cytokine levels peaked on day 5, followed by a decline on day 8. Wound exudation, measured by protein content, increased from day 2, peaking on day 5. The neutrophil-derived proteins myeloperoxidase, elastase, and heparin-binding protein (HBP) peaked on day 5, correlating with interleukin (IL)-8, a key neutrophil chemoattractant. The identified bacteria consisted primarily of commensal bacteria, including various staphylococci. Levels of such bacteria rose from day 2, peaking on days 5-8, and aligned with increases in the cytokines tumor necrosis factor α, IL-1β, and IL-10 at the peak of inflammation on day 5.
This study uncovers the coordinated dynamics of cytokines, neutrophil activity, and major commensal bacteria in epidermal wound healing and identifies HBP-a marker for neutrophil activation and endothelial leakage-for the first time in normally healing epidermal wounds.
炎症是伤口愈合所必需的；然而，其在正常愈合的表皮伤口中的动态变化尚未完全明确。为此，我们分析了从健康志愿者的表皮抽吸水疱伤口收集的纵向伤口液样本。
采用抽吸水疱法在24名健康志愿者（每条大腿1名）身上共诱导产生48个对照伤口。应用免疫测定、基质辅助激光解吸电离飞行时间质谱和微生物学方法，分析表皮伤口愈合过程中伤口拭子和敷料中的细胞因子动态、中性粒细胞活性、细菌定植及水平，重点关注可培养的活伤口细菌。
细胞因子水平在第5天达到峰值，随后在第8天下降。以蛋白质含量衡量的伤口渗出液从第2天开始增加，在第5天达到峰值。中性粒细胞衍生蛋白髓过氧化物酶、弹性蛋白酶和肝素结合蛋白（HBP）在第5天达到峰值，与关键的中性粒细胞趋化因子白细胞介素（IL）-8相关。鉴定出的细菌主要由共生菌组成，包括各种葡萄球菌。此类细菌的水平从第2天开始上升，在第5 - 8天达到峰值，并与炎症高峰期（第5天）细胞因子肿瘤坏死因子α、IL - 1β和IL - 10的增加一致。
本研究揭示了表皮伤口愈合过程中细胞因子、中性粒细胞活性和主要共生菌的协同动态变化，并首次在正常愈合的表皮伤口中鉴定出HBP——一种中性粒细胞活化和内皮渗漏的标志物。
