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A role for Syk-kinase in the control of the binding cycle of the β2 integrins (CD11/CD18) in human polymorphonuclear neutrophils

By Thomas Willeke, Jürgen Schymeinsky, Peggy Prange, Stefan Zahler and Barbara Walzog


A fine control of β2 integrin (CD11/CD18)-mediated firm adhesion of human neutrophils to the endothelial cell monolayer is required to allow ordered emigration. To elucidate the molecular mechanisms that control this process, intracellular protein tyrosine signaling subsequent to β2 integrin-mediated ligand binding was studied by immunoprecipitation and Western blotting techniques. The 72-kDa Syk-kinase, which was tyrosine-phosphorylated upon adhesion, was found to coprecipitate with CD18, the β-subunit of the β2 integrins. Moreover, inhibition of Syk-kinase by piceatannol enhanced adhesion and spreading but diminished N-formyl-Met-Leu-Phe-induced chemotactic migration. The enhancement of adhesiveness was associated with integrin clustering, which results in increased integrin avidity. In contrast, piceatannol had no effect on the surface expression or on the affinity of β2 integrins. Altogether, this suggests that Syk-kinase controls alternation of β2 integrin-mediated ligand binding with integrin detachment.

Topics: Chemie und Pharmazie, ddc:540
Year: 2003
DOI identifier: 10.1189/jlb.0102016
OAI identifier:
Provided by: Open Access LMU

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  6. (1981). A rapid method for purification of human granulocytes using Percoll. A comparison with dextran sulfate. doi
  7. (1993). A subpopulation of Mac-1 (CD11b/ CD18) molecules mediates neutrophil adhesion to ICAM-1 and fibrinogen. doi
  8. (1996). Activation of SRC family kinases in human neutrophils. Evidence that p58 C-FGR and p53/56 LYN redistributed to a Triton X-100-insoluble cytoskeletal fraction, also enriched in the caveolar protein Caveolin, display an enhanced kinase activity. doi
  9. (1992). Antibody against the Leu-CAM -chain (CD18) promotes both LFA-1-dependent and CR3-dependent adhesion events. doi
  10. (2000). Avidity regulation of integrins: the driving force in leukocyte adhesion. doi
  11. (1996). c-Cbl is downstream of c-Src in a signalling pathway necessary for bone resorption. doi
  12. (1995). Ca 2- and calcineurin-dependent recycling of an integrin to the front of migrating neutrophils. doi
  13. (1997). Caveolae, DIGs, and the dynamics of sphingolipid-cholesterol microdomains. doi
  14. (1991). CD11c/CD18 recognizes a domain at the N-terminus of the A-alpha chain of fibrinogen. doi
  15. (1991). Characterization of ICAM-2 and evidence for a third counterreceptor for LFA-1.
  16. (1970). Cleavage of structural proteins during assembly of the head of bacteriophage T4. doi
  17. (1996). Competition between lymphocyte function-associated antigen 1 (CD11a/CD18) and Mac-1 (CD11b/CD18) for binding to intercellular adhesion molecule-1 (CD54).
  18. (1988). Complement receptor type 3 (CD11b/CD18) of human polymorphonuclear leukocytes recognizes fibrinogen. doi
  19. (1994). Cross-linking of CD18 in human neutrophils induces an increase of intracellular free Ca 2, exocytosis of azurophilic granules, quantitative up-regulation of CD18, shedding of L-selectin, and actin polymerization.
  20. (1989). Cytokine-induced respiratory burst of human neutrophils: dependence on extracellular matrix proteins and CD11/CD18 integrins. doi
  21. (1984). Deficiency of a leukocyte surface glycoprotein (LFA-1) in two patients with Mo1 deficiency. Effects of cell activation on Mo1/LFA-1 surface expression in normal and deficient leukocytes. doi
  22. (1999). Focal adhesion motility revealed in stationary fibroblasts. doi
  23. (1997). Functional rafts in cell membranes. doi
  24. (2003). G-protein-coupled receptor signaling in Syk-deficient neutrophils and mast cells. doi
  25. (1990). Human neutrophil adherence to laminin in vitro.
  26. (1990). ICAM-1 (CD54): a counter-receptor for Mac-1 (CD11b/CD18).
  27. (1983). Identification of the C3bi receptor of human monocytes and macrophages by using monoclonal antibodies. doi
  28. (2001). Inhibition of beta 2 integrin receptor and Syk kinase signaling in monocytes by the Src family kinase Fgr. doi
  29. (1994). Inhibition of mast cell Fc epsilon R1-mediated signaling and effector function by the syk-selective inhibitor,
  30. (1999). Integrin leukocyte function-associated antigen-1-mediated cell binding can be activated by clustering of membrane rafts. doi
  31. (1995). Integrins and signal transduction pathways: the road taken. doi
  32. (1992). Integrins: versatility, modulation, and signaling in cell adhesion. doi
  33. (1997). LFA-1 is sufficient in mediating neutrophil emigration in Mac-1-deficient mice. doi
  34. (1988). Lymphocyte function associated antigen-1 (LFA-1) interaction with intercellular adhesion molecule-1 (ICAM-1) is one of at least three mechanisms for lymphocyte adhesion to cultured endothelial cells. doi
  35. (2000). Phosphorylation of Syk activation loop tyrosines is essential for Syk function. An in vivo study using a specific anti-Syk activation loop phosphotyrosine antibody. doi
  36. (1989). Piceatannol (3,4,3,5-tetrahydroxy-trans-stilbene) is a naturally occurring protein-tyrosine kinase inhibitor. doi
  37. (1997). Signaling by adhesion in human neutrophils–activation of the p72 syk tyrosine kinase and formation of protein complexes containing p72 syk and Src family kinases in neutrophils spreading over fibrinogen.
  38. (1990). Structure and function of the leukocyte adhesion molecules CD11/CD18. doi
  39. (2002). Syk is required for integrin signaling in neutrophils. doi
  40. (1997). Syk kinase activation by src kinase-initiated activation loop phosphorylation chain reaction. doi
  41. (1999). The actin cytoskeleton regulates LFA-1 ligand binding through avidity rather than affinity changes. doi
  42. (1995). The leukocyte integrin Mac-1 (CD11b/CD18) contributes to binding of human granulocytes to collagen. doi
  43. (1994). The leukocyte integrin p150,95 (CD11c/CD18) as a receptor for iC3b: activation by a heterologous subunit and localization of a ligand recognition site to the I domain.
  44. (2002). The N-terminal SH2 domains of Syk and ZAP-70 mediate phosphotyrosine-independent binding to integrin cytoplasmic domains. doi
  45. (1997). The product of the proto-oncogene c-cbl: a negative regulator of the Syk tyrosine kinase. doi
  46. (1997). The proto-oncogene product p120 cbl links c-Src and phosphatidylinositol 3-kinase to the integrin signaling pathway. doi
  47. (1994). Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. doi

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