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  3. Medizin - Open Access LMU - Teil 15/22 Podcast
  4. Spleen tyrosine kinase Syk is critical for sustained leukocyte adhesion during inflammation in vivo
Background: During inflammation, beta(2)-integrins mediate
leukocyte adhesion to the endothelium accompanied by the activation
of the spleen tyrosine kinase Syk. Results: We investigated
leukocyte adhesion and rolling in cremaster muscle venules before
and during stimulation with fMLP using mice with a Syk(-/-)
hematopoietic system. In unstimulated venules, Syk(-/-) leukocytes
adhered less efficiently than control leukocytes while rolling was
similar between Syk(-/-) and control leukocytes. During
fMLP-superfusion, control mice showed significantly increased
adhesion accompanied by reduced rolling. For Syk(-/-) leukocytes,
an increase in adhesion with a concomitant decrease in rolling was
only observed during the first three minutes during fMLP
stimulation, but not at later time points. We also investigated
leukocyte spreading against the vessel wall during fMLP stimulation
and found a significant impairment of spreading for Syk(-/-)
leukocytes. Additional in vitro experiments revealed that the
adhesion and spreading defect seen in Syk(-/-) chimeric mice was
due to compromised beta(2)-integrin-mediated outside-in signaling.
Conclusion: We provide substantial evidence for an important role
of Syk in mediating beta(2)-integrin dependent outside-in signaling
leading to sustained leukocyte adhesion and spreading during the
inflammatory response in vivo.

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