Cutting Edge: Evidence for a Signaling Partnership Between Urokinase Receptors (CD87) and L-Selectin (CD62L) in Human Polymorphonuclear Neutrophils

Leukocyte urokinase plasminogen activator receptors (uPARs) cluster at adhesion interfaces and at migratory fronts where they participate in adhesion, chemotaxis, and proteolysis. uPAR aggregation triggers activation signaling even though this glycolipid-anchored protein must associate with membrane...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2001-04, Vol.166 (8), p.4822-4825
Main Authors: Sitrin, Robert G, Pan, Pauline M, Blackwood, R. Alexander, Huang, Jibiao, Petty, Howard R
Format: Article
Language:English
Subjects:
Carbohydrate Metabolism
Cell Adhesion - immunology
Energy Transfer - immunology
Glycosylation
Humans
L-Selectin - immunology
L-Selectin - metabolism
L-Selectin - physiology
Ligands
Neutrophil Activation - immunology
Neutrophils - enzymology
Neutrophils - immunology
Neutrophils - metabolism
Protein Binding - immunology
Protein Structure, Tertiary
Receptors, Cell Surface - physiology
Receptors, Urokinase Plasminogen Activator
Signal Transduction - immunology
Spectrometry, Fluorescence
Urokinase-Type Plasminogen Activator - metabolism
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Summary:Leukocyte urokinase plasminogen activator receptors (uPARs) cluster at adhesion interfaces and at migratory fronts where they participate in adhesion, chemotaxis, and proteolysis. uPAR aggregation triggers activation signaling even though this glycolipid-anchored protein must associate with membrane-spanning proteins to access the cell interior. This study demonstrates a novel partnership between uPAR and L-selectin in human polymorphonuclear neutrophils. Fluorescence resonance energy transfer demonstrated a direct physical association between uPAR and L-selectin. To examine the role of L-selectin in uPAR-mediated signaling, uPAR was cross-linked and intracellular Ca(2+) concentrations were measured by spectrofluorometry. A mAb reactive against the carbohydrate binding domain (CBD) of L-selectin substantially inhibited uPAR-mediated Ca(2+) mobilization, whereas mAbs against the beta(2) integrin complement receptor 3 (CR3), another uPAR-binding adhesion protein, had no effect. Similarly, fucoidan, a sulfated polysaccharide that binds to L-selectin CBD, inhibited the Ca(2+) signal. We conclude that uPAR associates with the CBD region of L-selectin to form a functional signaling complex.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.166.8.4822