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Sci. Signal., 6 September 2011
[DOI: 10.1126/scisignal.2001811]

Supplementary Materials for:

Small Molecule–Mediated Activation of the Integrin CD11b/CD18
Reduces Inflammatory Disease

Dony Maiguel, Mohd Hafeez Faridi, Changli Wei, Yoshihiro Kuwano, Keir M. Balla, Dayami Hernandez, Constantinos J. Barth, Geanncarlo Lugo, Mary Donnelly, Ali Nayer, Luis F. Moita, Stephan Schürer, David Traver, Phillip Ruiz, Roberto I. Vazquez-Padron, Klaus Ley, Jochen Reiser, Vineet Gupta*

*To whom correspondence should be addressed. E-mail: vgupta2{at}med.miami.edu

This PDF file includes:

  • Fig. S1. Leukadherins are true agonists and do not inhibit cell adhesion in the presence of the agonist Mn2+.
  • Fig. S2. Leukadherins do not affect the surface abundance of CD11b/CD18 on K562 cells.
  • Fig. S3. Leukadherins do not mobilize CD11b/CD18 from internal pools or affect the amount of CD11b/CD18 on the surface of human neutrophils.
  • Fig. S4. Leukadherins increase the adhesion of CD11b/CD18-expressing cells to iC3b.
  • Fig. S5. Leukadherin-dependent CD11b/CD18 activation is independent of ligand type.
  • Fig. S6. Leukadherin-dependent activation of CD11b/CD18 occurs in THP-1 cells.
  • Fig. S7. Leukadherins increase the extent of binding of iC3b-coated RBCs by K562 cells.
  • Fig. S8. Ribbon diagrams showing computational models for the binding of LA1 and LA2 in an activation-sensitive region of the CD11b A domain.
  • Fig. S9. Leukadherins activate full-length CD11b/CD18 on live K562 cells.
  • Fig. S10. Leukadherins have a higher affinity than does IMB-10 for CD11b/CD18.
  • Fig. S11. Leukadherins do not affect neutrophil migration in 3D gels in vitro.
  • Fig. S12. Leukadherins do not cause cytotoxicity in vitro.
  • Fig. S13. Leukadherins do not cause neutrophil cytotoxicity in vitro.
  • Fig. S14. Leukadherins do not induce integrin clustering or outside-in signaling.
  • Fig. S15. Leukadherins do not induce CD11b/CD18-mediated outside-in signaling.
  • Fig. S16. The control compound LA-C has no effect on neointimal thickening upon balloon injury in wild-type rats.
  • Fig. S17. LA3 substantially reduces neointimal thickening after balloon injury in rats.
  • Fig. S18. LA2 prevents neutrophil recruitment to injured tissue in a reversible manner.
  • Fig. S19. Leukadherins do not lead to loss of neutrophil numbers in zebrafish larvae.
  • Fig. S20. Leukadherins reduce the number of transmigrated cells in vivo.
  • Table S1. White blood cell counts in mouse whole-blood samples.
  • Descriptions for Movies S1 to S8
  • References

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Technical Details

Format: Adobe Acrobat PDF

Size: 1.59 MB

Other Supplementary Material for this manuscript includes the following:

  • Movie S1 (.mov format). Neutrophil chemotaxis in 2D in the presence of DMSO (control).
  • Movie S2 (.mov format). Neutrophil chemotaxis in 2D in the presence of LA1.
  • Movie S3 (.mov format). Neutrophil chemotaxis in 2D in the presence of LA2.
  • Movie S4 (.mov format). Neutrophil chemotaxis in 2D in the presence of LA3.
  • Movie S5 (.mov format). Neutrophil migration in 3D networks in vitro in the presence of DMSO (control).
  • Movie S6 (.mov format). Neutrophil migration in 3D networks in vitro in the presence of LA1.
  • Movie S7 (.avi format). Intravital microscopy in TNF-α–treated cremaster muscle with LA1.
  • Movie S8 (.avi format). Intravital microscopy in TNF-α–treated cremaster muscle with LA1 and the mAb M1/70.

Citation: D. Maiguel, M. H. Faridi, C. Wei, Y. Kuwano, K. M. Balla, D. Hernandez, C. J. Barth, G. Lugo, M. Donnelly, A. Nayer, L. F. Moita, S. Schürer, D. Traver, P. Ruiz, R. I. Vazquez-Padron, K. Ley, J. Reiser, V. Gupta, Small Molecule–Mediated Activation of the Integrin CD11b/CD18 Reduces Inflammatory Disease. Sci. Signal. 4, ra57 (2011).

© 2011 American Association for the Advancement of Science


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