The role of chemoattractants in modulating neutrophil-endothelial adhesion
The role of chemoattractants in modulating neutrophil-endothelial adhesion
This study aimed to define the role of IL-8 and other chemoattractants in neutrophil recruitment to sites of inflammation, and in particular, to characterise the mechanisms by which chemoattractants, when present in the luminal compartment, may modulate neutrophil--endothelial adhesion under conditions of flow.
In vitro models of inflammation were employed including a flow chamber which stimulated the pathophysiological conditions of flow at the apical endothelial surface in vivo and a Boyden-type chemotaxis assay. The effect of chemoattractants when presented in different ways to neutrophils on the dynamics of their adhesion under flow, adhesion molecule expression and chemotaxis, were examined.
Activated endothelium secreted soluble IL-8 but neither IL-8 nor platelet-activating factor (PAF) was necessary for neutrophil rolling, adhesion and transmigration on activated endothelium. Prior exposure of neutrophils to nanomolar concentrations of IL-8 or PAF induced L-selectin shedding and reduced ability to tether and roll on activated endothelium. IL-8 and other peptide chemoattractants but not PAF, induced detachment of neutrophils stably adherent to activated endothelium. Furthermore, nanomolar concentrations of IL-8 and other peptide chemoattractants in the apical compartment totally inhibited neutrophil transmigration.
Therefore, chemoattractants appeared to modulate neutrophil-endothelial adhesion in different ways depending on how they were presented to neutrophils. The environment in the sub-endothelial compartment allows chemoattractants to accumulate and to generate a chemotactic gradient which may promote neutrophil recruitment. However, a high concentration of IL-8 in the apical compartment does not appear to be an appropriate physiological signal for neutrophil recruitment at sites of inflammation and may inhibit neutrophil-endothelial adhesion and transmigration by a number of mechanisms.
University of Southampton
1999
Tan, Peter Swee Chuan
(1999)
The role of chemoattractants in modulating neutrophil-endothelial adhesion.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
This study aimed to define the role of IL-8 and other chemoattractants in neutrophil recruitment to sites of inflammation, and in particular, to characterise the mechanisms by which chemoattractants, when present in the luminal compartment, may modulate neutrophil--endothelial adhesion under conditions of flow.
In vitro models of inflammation were employed including a flow chamber which stimulated the pathophysiological conditions of flow at the apical endothelial surface in vivo and a Boyden-type chemotaxis assay. The effect of chemoattractants when presented in different ways to neutrophils on the dynamics of their adhesion under flow, adhesion molecule expression and chemotaxis, were examined.
Activated endothelium secreted soluble IL-8 but neither IL-8 nor platelet-activating factor (PAF) was necessary for neutrophil rolling, adhesion and transmigration on activated endothelium. Prior exposure of neutrophils to nanomolar concentrations of IL-8 or PAF induced L-selectin shedding and reduced ability to tether and roll on activated endothelium. IL-8 and other peptide chemoattractants but not PAF, induced detachment of neutrophils stably adherent to activated endothelium. Furthermore, nanomolar concentrations of IL-8 and other peptide chemoattractants in the apical compartment totally inhibited neutrophil transmigration.
Therefore, chemoattractants appeared to modulate neutrophil-endothelial adhesion in different ways depending on how they were presented to neutrophils. The environment in the sub-endothelial compartment allows chemoattractants to accumulate and to generate a chemotactic gradient which may promote neutrophil recruitment. However, a high concentration of IL-8 in the apical compartment does not appear to be an appropriate physiological signal for neutrophil recruitment at sites of inflammation and may inhibit neutrophil-endothelial adhesion and transmigration by a number of mechanisms.
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Published date: 1999
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Local EPrints ID: 463987
URI: http://eprints.soton.ac.uk/id/eprint/463987
PURE UUID: 7a444278-3ab6-4680-b61a-d8e84d305c23
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Date deposited: 04 Jul 2022 21:00
Last modified: 04 Jul 2022 21:00
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Author:
Peter Swee Chuan Tan
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