Neutrophil-mediated protection of cultured human vascular endothelial cells
from damage by growing Candida albicans hyphae
JE Edwards , D Rotrosen, JW Fontaine, CC Haudenschild and RD Diamond
Interactions were studied between human neutrophils and cultured human
umbilical vein endothelial cells invaded by Candida albicans. In the
absence of neutrophils, progressive Candida germination and hyphal growth
extensively damaged endothelial cell monolayers over a period of 4 to 6
hours, as determined both by morphological changes and release of 51Cr from
radiolabeled endothelial cells. Monolayers were completely destroyed and
replaced by hyphae after 18 hours of incubation. In contrast, when added 2
hours after the monolayers had been infected with Candida, neutrophils
selectively migrated toward and attached to hyphae at points of hyphal
penetration into individual endothelial cells (observed by time-lapse
video-microscopy). Attached neutrophils spread over hyphal surfaces both
within and beneath the endothelial cells; neutrophil recruitment to initial
sites of leukocyte-Candida- endothelial cell interactions continued
throughout the first 60 minutes of observation. Neutrophil spreading and
stasis were observed only along Candida hyphae and at sites of
Candida-endothelial cell interactions. These events resulted in 58.0%
killing of Candida at 2 hours and subsequent clearance of Candida from
endothelial cell monolayers, as determined by microcolony counts and
morphological observation. On introduction of additional neutrophils to
yield higher ratios of neutrophils to endothelial cells (10 neutrophils:1
endothelial cell), neutrophil migration toward hyphal elements continued.
Despite retraction or displacement of occasional endothelial cells by
invading Candida and neutrophils, most endothelial cells remained intact,
viable, and motile as verified both by morphological observations and
measurement of 51Cr release from radiolabeled monolayers. From these
studies, we conclude that neutrophils are capable of killing Candida hyphae
selectively within human vascular endothelial cell monolayers and may have
protective rather than detrimental effects on endothelial cell integrity.
Volume 69,
Issue 5,
pp. 1450-1457,
05/01/1987
Copyright © 1987 by The American Society of Hematology
