Spleen tyrosine kinase Syk is critical for sustained leukocyte adhesion during inflammation in vivo.
BACKGROUND
During inflammation, beta2-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 beta2-integrin-mediated outside-in signaling.


CONCLUSIONS
We provide substantial evidence for an important role of Syk in mediating beta2-integrin dependent outside-in signaling leading to sustained leukocyte adhesion and spreading during the inflammatory response in vivo.
Frommhold
David
D
Children's Hospital, Neonatal Unit, University of Heidelberg, Germany. davidfrommhold@web.de
Mannigel
Ingrid
I
Schymeinsky
Jürgen
J
Mocsai
Attila
A
Poeschl
Johannes
J
Walzog
Barbara
B
Sperandio
Markus
M
D000818:Animals; D018821:CD18 Antigens / Q000276:immunology / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism*; D036904:Leukocyte Rolling / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D018482:Muscle, Skeletal / Q000098:blood supply; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000633:toxicity; D011505:Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism*; D000072377:Syk Kinase; D018183:Transplantation Chimera; D014699:Venules / Q000276:immunology
D018821:CD18 Antigens; D047908:Intracellular Signaling Peptides and Proteins; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse