| Summary: | <p>Abstract</p> <p>Background</p> <p>During inflammation, β<sub>2</sub>-integrins mediate leukocyte adhesion to the endothelium accompanied by the activation of the spleen tyrosine kinase Syk.</p> <p>Results</p> <p>We investigated leukocyte adhesion and rolling in cremaster muscle venules before and during stimulation with fMLP using mice with a <it>Syk</it><sup>-/- </sup>hematopoietic system. In unstimulated venules, <it>Syk</it><sup>-/- </sup>leukocytes adhered less efficiently than control leukocytes while rolling was similar between <it>Syk</it><sup>-/- </sup>and control leukocytes. During fMLP-superfusion, control mice showed significantly increased adhesion accompanied by reduced rolling. For <it>Syk</it><sup>-/- </sup>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 <it>Syk</it><sup>-/- </sup>leukocytes. Additional in vitro experiments revealed that the adhesion and spreading defect seen in <it>Syk</it><sup>-/- </sup>chimeric mice was due to compromised β<sub>2</sub>-integrin-mediated outside-in signaling.</p> <p>Conclusion</p> <p>We provide substantial evidence for an important role of Syk in mediating β<sub>2</sub>-integrin dependent outside-in signaling leading to sustained leukocyte adhesion and spreading during the inflammatory response in vivo.</p>
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