Human endothelial cells regulate polymorphonuclear leukocyte degranulation.
Neutrophil degranulation is an important event in inflammatory responses. We examined the regulation of neutrophil (PMN) degranulation by resting and activated human endothelial cells. Whereas PMNs adherent to endothelial cells that were stimulated to express P-selectin and platelet-activating factor did not release the specific granule marker lactoferrin or the primary granule enzyme, elastase, PMNs adherent to endothelial cells stimulated with interleukin-1 (IL-1) or tumor necrosis factor secreted both. PMN degranulation was dependent on the time of incubation of endothelial cells with the cytokine, its concentration, and the time of incubation of the PMNs with endothelial cells. Degranulation of PMNs and their adhesion to stimulated endothelial cells are correlated events, but they could be dissociated by blocking the tethering molecules used by the endothelial cells and neutrophils under these conditions. This suggested that paracrine signaling molecules that induce PMN degranulation are produced by cytokine-stimulated endothelial cells. We found that endothelial cells stimulated with IL-1 release newly synthesized degranulating factors that require transcription and translation. IL-8 was synthesized, released, and signaled granular secretion by PMNs. However, experiments with blocking antibodies indicated the presence of an additional degranulating factor not accounted for by IL-8. These experiments demonstrate that human endothelial cells regulate degranulation of neutrophils by generating signaling factors that are expressed differentially depending on the endothelial agonist and other features. Active modification of neutrophil granular secretion by endothelial cells can influence physiologic acute inflammatory responses but may also contribute to pathologic vascular and tissue damage.
Topham
M K
MK
Nora Eccles Harrison Cardiovascular Research and Training Institute, Department of Medicine, University of Utah School of Medicine, Salt Lake City 84112-5000, USA.
Carveth
H J
HJ
McIntyre
T M
TM
Prescott
S M
SM
Zimmerman
G A
GA
D002448:Cell Adhesion; D015550:Cell Degranulation / Q000502:physiology*; D016207:Cytokines / Q000494:pharmacology; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism; D007781:Lactoferrin / Q000378:metabolism; D019272:Leukocyte Elastase / Q000378:metabolism; D018375:Neutrophil Activation / Q000502:physiology*; D019007:P-Selectin / Q000378:metabolism; D019899:Paracrine Communication
D016207:Cytokines; D019040:E-Selectin; D007375:Interleukin-1; D016209:Interleukin-8; D019007:P-Selectin; D007781:Lactoferrin; D019272:Leukocyte Elastase