Activated neutrophils disrupt endothelial monolayer integrity by an oxygen radical-independent mechanism
The effect of activated neutrophils on endothelial monolayer integrity in vitro has been measured by assessing the capacity of endothelial monolayers on polycarbonate filters to exclude /sup 125/I-albumin. Although formylmethionyl-leucyl-phenylalanine (FMLP)-activated neutrophils failed to induce /sup 51/Cr-release or detachment after 4 hours of incubation with endothelial monolayers cultured in polystyrene wells, FMLP-activated neutrophils produced a marked increase in the passage of /sup 125/I-albumin across bovine aortic or pulmonary artery endothelial monolayers on polycarbonate filters. This effect was evident as early as 30 minutes following the addition of FMLP-activated neutrophils to the monolayer and reached 180% over control values at 2 hours (p . 0.001). Light and transmission electron microscopic examination of the polycarbonate filters exposed to FMLP-activated neutrophils revealed focal disruption of the endothelial monolayers. Chronic granulomatous disease neutrophils produced similar disruption of the endothelial monolayer at 2 hours. Moreover, catalase and superoxide dismutase failed to reduce significantly the neutrophil-mediated increase in /sup 125/I-albumin passage at 2 hours. Cell-free postsecretory supernatants of FMLP-activated neutrophils, leukotriene C4, and platelet activating factor did not induce a significant increase in /sup 125/I-albumin passage across the endothelial monolayers. Of note, FMLP-activated neutrophils from a patient with a congenital abnormality of neutrophil adhesion and chemotaxis did not induce disruption of the monolayer or increase /sup 125/I-albumin passage.
- Research Organization:
- Univ. of Washington, Seattle
- OSTI ID:
- 5607930
- Journal Information:
- Lab. Invest.; (United States), Vol. 52:2
- Country of Publication:
- United States
- Language:
- English
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ADHESION
ALBUMINS
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CATALASE
CATTLE
CHROMIUM 51
ELECTRON MICROSCOPY
IODINE 125
LABELLED COMPOUNDS
OXYGEN
PHENYLALANINE
SUPEROXIDE DISMUTASE
TRACER TECHNIQUES
AMINO ACIDS
ANIMAL TISSUES
ANIMALS
BETA DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
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CARDIOVASCULAR SYSTEM
CHROMIUM ISOTOPES
DAYS LIVING RADIOISOTOPES
DOMESTIC ANIMALS
ELECTRON CAPTURE RADIOISOTOPES
ELEMENTS
ENZYMES
EVEN-ODD NUCLEI
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
INTERMEDIATE MASS NUCLEI
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LEUKOCYTES
MAMMALS
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ORGANIC NITROGEN COMPOUNDS
ORGANS
OXIDOREDUCTASES
PEROXIDASES
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RADIOISOTOPES
RUMINANTS
TISSUES
VERTEBRATES
551001* - Physiological Systems- Tracer Techniques