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

Longkun Zhu, Pingnian He

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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
Volume290
Issue number1
DOIs
StatePublished - Jan 1 2006

Fingerprint

methionyl-leucyl-phenylalanine
Microvessels
Permeability
Reactive Oxygen Species
Leukocytes
Neutrophils
Respiratory Burst
Perfusion
Luminescent Measurements
Deferoxamine
Mesentery
Chelating Agents
Superoxide Dismutase
hydroxide ion
Inflammation

All Science Journal Classification (ASJC) codes

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

Cite this

@article{bd8c4c6b012f4793ae5c2f7f99617e82,
title = "fMLP-stimulated release of reactive oxygen species from adherent leukocytes increases microvessel permeability",
abstract = "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.",
author = "Longkun Zhu and Pingnian He",
year = "2006",
month = "1",
day = "1",
doi = "10.1152/ajpheart.00812.2005",
language = "English (US)",
volume = "290",
pages = "H365--H372",
journal = "American Journal of Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "1",

}

TY - JOUR

T1 - fMLP-stimulated release of reactive oxygen species from adherent leukocytes increases microvessel permeability

AU - Zhu, Longkun

AU - He, Pingnian

PY - 2006/1/1

Y1 - 2006/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33644792606&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33644792606&partnerID=8YFLogxK

U2 - 10.1152/ajpheart.00812.2005

DO - 10.1152/ajpheart.00812.2005

M3 - Article

C2 - 16155097

AN - SCOPUS:33644792606

VL - 290

SP - H365-H372

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6135

IS - 1

ER -