Oxidative stress during platelet-activating factor-induced microvascular dysfunction.
OBJECTIVE
To assess the potential contribution of hydrogen peroxide (H2O2) to the leukocyte-endothelial cell adhesion and increased microvascular permeability (to fluorescein isothiocyanate [FITC]-albumin) observed in rat mesenteric venules exposed to platelet-activating factor (PAF).


METHODS
The production of oxidants derived from H2O2 in mesenteric tissue was monitored using the H2O2-sensitive fluorochrome, dihydrorhodamine 123 (DHR). PAF elicited a rapid increase in both the albumin extravasation and oxidation of DHR, which was followed by an increased adherence and emigration of leukocytes in postcapillary venules.


RESULTS
The PAF-induced oxidation of DHR, leukocyte-endothelial cells interactions, and albumin leakage were attenuated by treatment with either catalase or dimethylthiourea. Treatment with monoclonal antibody directed against either CD11b/CD18 on leukocytes or ICAM-1 on endothelial cells attenuated the PAF-induced oxidative stress, albumin leakage, and leukocyte-endothelial cell adhesion.


CONCLUSIONS
These findings indicate that most of the oxidants generated in mesenteric tissue exposed to PAF results from the accumulation of activated leukocytes.
Kurose
I
I
Department of Physiology, Louisiana State University Medical Center, Shreveport 71130-3932, USA.
Argenbright
L W
LW
Wolf
R
R
Granger
D N
DN
D000818:Animals; D000911:Antibodies, Monoclonal; D002199:Capillary Permeability / Q000187:drug effects*; D002374:Catalase / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D008643:Mesentery / Q000098:blood supply*; D008833:Microcirculation / Q000502:physiology*; D018715:Microscopy, Video; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010972:Platelet Activating Factor / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012235:Rhodamines / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D010972:Platelet Activating Factor; D012235:Rhodamines; C039217:fluorescein isothiocyanate bovine serum albumin; C058319:dihydrorhodamine 123; D012710:Serum Albumin, Bovine; C038983:1,3-dimethylthiourea; D006861:Hydrogen Peroxide; D002374:Catalase; D013890:Thiourea; D016650:Fluorescein-5-isothiocyanate