Differential immobilization and hierarchical involvement of chemokines in monocyte arrest and transmigration on inflamed endothelium in shear flow

Differential immobilization and hierarchical involvement of chemokines in monocyte arrest and... Monocyte extravasation into areas of inflammation involves sequential interactions of multiple adhesion molecules. However, differential contribution of chemokines produced by cytokine‐stimulated endothelium and their receptors to leukocyte attachment and transmigration under flow conditions remains to be elucidated. The activation of endothelial cells with TNF‐α up‐regulated mRNA and protein expression of the CXC chemokine GRO‐α and the CC chemokine monocyte chemotactic protein (MCP)‐1, which act through the receptors CXCR2 and CCR2 expressed on monocytes, respectively. Whereas GRO‐α was immobilized to endothelial cells via heparan sulfate proteoglycans, MCP‐1 was secreted in a soluble form. Consequently, inhibition experiments with blocking peptide analogues and monoclonal antibodies revealed that GRO‐α and its receptor CXCR2 but not MCP‐1 and its receptors substantially contributed to conversion of rolling into firm, shear‐resistant arrest of monocytes to TNF‐α‐stimulated endothelium in physiological flow. In contrast, MCP‐1 and CCR2 but not GRO‐α and CXCR2 mediated spreading, shape change and subsequent transendothelial migration, which was evident in flow but rarely in stasis and may thus require the establishment of a diffusible MCP‐1 gradient. Differential patterns of presentation may determine a functional specialization and hierarchy of chemokines and their receptors in sequential steps of monocyte emigration on inflamed endothelium and shear flow. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Immunology Wiley

Differential immobilization and hierarchical involvement of chemokines in monocyte arrest and transmigration on inflamed endothelium in shear flow

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Publisher
Wiley
Copyright
© 1999 WILEY‐VCH Verlag GmbH, Weinheim, Fed. Rep. of Germany
ISSN
0014-2980
eISSN
1521-4141
D.O.I.
10.1002/(SICI)1521-4141(199902)29:02<700::AID-IMMU700>3.0.CO;2-1
Publisher site
See Article on Publisher Site

Abstract

Monocyte extravasation into areas of inflammation involves sequential interactions of multiple adhesion molecules. However, differential contribution of chemokines produced by cytokine‐stimulated endothelium and their receptors to leukocyte attachment and transmigration under flow conditions remains to be elucidated. The activation of endothelial cells with TNF‐α up‐regulated mRNA and protein expression of the CXC chemokine GRO‐α and the CC chemokine monocyte chemotactic protein (MCP)‐1, which act through the receptors CXCR2 and CCR2 expressed on monocytes, respectively. Whereas GRO‐α was immobilized to endothelial cells via heparan sulfate proteoglycans, MCP‐1 was secreted in a soluble form. Consequently, inhibition experiments with blocking peptide analogues and monoclonal antibodies revealed that GRO‐α and its receptor CXCR2 but not MCP‐1 and its receptors substantially contributed to conversion of rolling into firm, shear‐resistant arrest of monocytes to TNF‐α‐stimulated endothelium in physiological flow. In contrast, MCP‐1 and CCR2 but not GRO‐α and CXCR2 mediated spreading, shape change and subsequent transendothelial migration, which was evident in flow but rarely in stasis and may thus require the establishment of a diffusible MCP‐1 gradient. Differential patterns of presentation may determine a functional specialization and hierarchy of chemokines and their receptors in sequential steps of monocyte emigration on inflamed endothelium and shear flow.

Journal

European Journal of ImmunologyWiley

Published: Feb 1, 1999

References

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