The release of reactive oxidant species by FMLP-stimulated leukocytes increases microvessel permeability.
Zhu-L; Castranovo-V; He-P
FASEB J 2003 Mar; 17(4)(Part 1)(Suppl S):A137
Our previous study demonstrated that systemic application of TNF-alpha induced a significant leukocyte adhesion without increasing microvessel permeability. Our present study is to investigate the effect of fMLP-stimulated leukocytes on microvessel permeability. The ROS production upon neutrophil activation was quantified by measuring the changes in chemiluminescence (CL) using a luminometer. The peak CL signal increased 3.1 fold after exposure of isolated rat neutrophils (2 x 10(6)/ml) to fMLP (10 ÁM). Measurements of hydraulic conductivity (Lp) in single perfused rat mesenteric venular microvessels showed that perfusing the vessel with a fMLP-stimulated neutrophil suspension (2 x 10(7)/ml) increased Lp to 3.7 +/- 0.6 times the control (n=4). After adding fMLP (10 ÁM) to the perfusate (n=4) or superfusate (n=8) and perfusing the vessel under balance pressure for 5 min in the presence of TNF-alpha-induced adherent leukocytes (14 +/- 1/100 Ám), the mean peak Lp increased to 5.2 +/- 0.9 and 4.6 +/- 0.5 times control, respectively. The application of DFO, an iron chelator, attenuated the Lp increase to 1.5 +/- 0.2 times control (n=4). In contrast, neither TNF-alpha-induced leukocyte adhesion nor perfusing fMLP alone changed basal Lp. These results suggest that the fMLP-stimulated leukocytes increase microvessel permeability by increased ROS production, which is independent of leukocyte adhesion and migration processes.
Leukocytes; Genetics; Cell-wall-permeability; Neutrophils; Oxidative-processes; Chelating-agents; Microbiology
West Virginia University, Health Science Center, Morgantown, WV 26506
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