ACTIVATED NEUTROPHILS DISRUPT ENDOTHELIAL MONOLAYER INTEGRITY BY AN OXYGEN RADICAL-INDEPENDENT MECHANISM

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  • 1 January 1985
    • journal article
    • research article
    • Vol. 52  (2) , 141-150
Abstract
The effect of activated neutrophils on endothelial monolayer integrity in vitro was measured by assessing the capacity of endothelial monolayers on polycarbonate filters to exclude 125I-albumin. Although formylmethionyl-leucyl-phenylalanine (FMLP)-activated neutrophils failed to induce 51Cr-release or detachment after 4 h of incubation with endothelial monolayers cultured in polystyrene wells, FMLP-activated neutrophils produced a marked increase in the passage of 125I-albumin across bovine aortic or pulmonary artery endothelial monolayers on polycarbonate filters. This effect was evident as early as 30 min following the addition of FMLP-activated neutrophils to the monolayer and reached 180% over control values at 2 h (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 h. Catalase and superoxide dismutase failed to reduce significantly the neutrophil-mediated increase in 125I-albumin passage at 2 h. Cell-free postsecretory supernatants of FMLP-activated neutrophils, leukotriene C4 and platelet activating factor did not induce a significant increase in 125I-albumin passage across the endothelial monolayers. FMLP-activated neutrophils from a patient with a congenital abnormality of neutrophil adhesion and chemotaxis did not induce disruption of the monolayer or increase 125I-albumin passage. Evidently, activated neutrophils mediate rapid, nonlytic disruption of endothelial monlayer integrity by an oxygen radical-independent mechanism that requires neutrophil-endothelial contact.