title: The induction of vascular endothelial growth factor by ultrafine carbon black contributes to the increase of alveolar-capillary permeability.
abstract: Ultrafine carbon black (ufCB) can cause proinflammatory response and increase alveolar-capillary permeability. However, the mechanism underlying the increased permeability is not well characterized. Vascular endothelial growth factor (VEGF) is originally recognized as a vascular permeability factor. Oxidative stress generated by hydrogen peroxide (H2O2) stimulates VEGF gene expression. The purpose of this study was to explore the role of VEGF in ufCB-induced alveolar-capillary permeability. Intratracheal instillation of 200 microg ufCB in mice caused a significant and sustained increase of total proteins in bronchoalveolar lavage (BAL) fluid, with the maximal increase at 21 hr postinstillation. The influx of neutrophils did not significantly increase until 16 hr. It reached the highest level at 21 hr and returned to the basal level by 42 hr. Tumor necrosis factor-alpha was significantly elevated only at 4 hr. ufCB induced significant increases of VEGF in BAL fluid throughout the study period, with the peak increase at 16 hr. The nonsecreted isoform VEGF188 was not altered after 16 hr of exposure to ufCB. Moreover, there was a strong correlation between VEGF and total proteins in BAL fluid (R2 = 0.7352, p < 0.01). In vivo study supported the role of reactive oxygen species (ROSs) in ufCB-induced VEGF release and protein leakage. The involvement of ROSs was strengthened by the fact that interventions with N-acetylcysteine prevented ufCB-induced generation of ROSs and VEGF in vitro. Our study for the first time demonstrates that ufCB induces the production of VEGF, which is associated with the increase of alveolar-capillary permeability. The induction of VEGF by ufCB acts through an ROS-dependent pathway.
authors.affiliation: Graduate Institute of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chih-Ching
authors.initials: CC
authors.lastname: Chang
authors.forename: Hui-Fen
authors.initials: HF
authors.lastname: Chiu
authors.forename: Yih-Shyuan
authors.initials: YS
authors.lastname: Wu
authors.forename: Yi-Chih
authors.initials: YC
authors.lastname: Li
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Tsai
authors.forename: Chen-Kuo
authors.initials: CK
authors.lastname: Shen
authors.forename: Chun-Yuh
authors.initials: CY
authors.lastname: Yang
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002199:Capillary Permeability / Q000187:drug effects*; D002244:Carbon / Q000633:toxicity*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009504:Neutrophils / Q000378:metabolism; D010316:Particle Size; D011506:Proteins / Q000032:analysis; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042442:Vascular Endothelial Growth Factors / Q000096:biosynthesis
chemical_list: D011506:Proteins; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D042442:Vascular Endothelial Growth Factors; D002244:Carbon; D000111:Acetylcysteine