fMLP-stimulated release of reactive oxygen species from adherent leukocytes increases microvessel permeability

Longkun Zhu, Pingnian He

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33 Scopus citations


Our previous study (Am J Physiol Heart Circ Physiol 288: H1331-H1338, 2005) demonstrated that TNF-α induced significant leukocyte adhesion without causing increases in microvessel permeability, and that formyl-Met-Leu-Phe-OH (fMLP)-stimulated neutrophils in the absence of adhesion increased microvessel permeability via released reactive oxygen species (ROS). The objective of our present study is to investigate the mechanisms that regulate neutrophil respiratory burst and the roles of fMLP-stimulated ROS release from adherent leukocytes in microvessel permeability. A technique that combines single-microvessel perfusion with autologous blood perfusion was employed in venular microvessels of rat mesenteries. Leukocyte adhesion was induced by systemic application of TNF-α. Microvessel permeability was assessed by measuring hydraulic conductivity (Lp). The 2-h autologous blood perfusion after TNF-α application increased leukocyte adhesion from 1.2 ± 0.2 to 13.3 ± 1.6 per 100 μm of vessel length without causing increases in Lp. When fMLP (10 μM) was applied to either perfusate (n = 5) or superfusate (n = 8) in the presence of adherent leukocytes, Lp transiently increased to 4.9 = 0.9 and 4.4 ± 0.3 times the control value, respectively. Application of superoxide dismutase or an iron chelator, deferoxamine mesylate, after fMLP application prevented or attenuated the Lp increase. Chemiluminescence measurements in isolated neutrophils demonstrated that TNF-α alone did not induce ROS release but that preexposure of neutrophils to TNF-α in vivo or in vitro potentiated fMLP-stimulated ROS release. These results suggest a priming role of TNF-α in fMLP-stimulated neutrophil respiratory burst and indicate that the released ROS play a key role in leukocyte-mediated permeability increases during acute inflammation.

Original languageEnglish (US)
Pages (from-to)H365-H372
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number1
StatePublished - Jan 2006

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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