Supplementary Materials

Supplementary Material for:

Chemokine interactome mapping enables tailored intervention in acute and chronic inflammation

Philipp von Hundelshausen, Stijn M. Agten, Veit Eckardt, Xavier Blanchet, Martin M. Schmitt, Hans Ippel, Carlos Neideck, Kiril Bidzhekov, Julian Leberzammer, Kanin Wichapong, Alexander Faussner, Maik Drechsler, Jochen Grommes, Johanna P. van Geffen, He Li, Almudena Ortega-Gomez, Remco T. A. Megens, Ronald Naumann, Ingrid Dijkgraaf, Gerry A. F. Nicolaes, Yvonne Döring, Oliver Soehnlein, Esther Lutgens, Johan W. M. Heemskerk, Rory R. Koenen, Kevin H. Mayo, Tilman M. Hackeng, Christian Weber*

*Corresponding author. Email: chweber{at}

Published 5 April 2017, Sci. Transl. Med. 9, eaah6650 (2017)
DOI: 10.1126/scitranslmed.aah6650

This PDF file includes:

  • Materials and Methods
  • Fig. S1. Representative ligand blot and densitometric values.
  • Fig. S2. Interaction of CCL5 and CCL5E66S with CCL17 analyzed by SPR.
  • Fig. S3. CXCL4K50E- and CCL17-induced changes in the HSQC spectrum of CCL5E66S.
  • Fig. S4. Chemical shift and resonance intensity changes of CCL5E66S residues.
  • Fig. S5. CXCL4K50E-induced changes in the HSQC spectrum of CCL5.
  • Fig. S6. Concentration-dependent formation of CC- versus CXC-type heterodimers.
  • Fig. S7. CCL5-induced changes in HSQC spectra of CXCL12.
  • Fig. S8. Structural models of CC-type and CXC-type heterodimers.
  • Fig. S9. Targeting of CCL5-CXCL4 heterodimer by CKEY.
  • Fig. S10. Interaction of CAN with CCL17.
  • Fig. S11. Targeting of CCL5-CCL17 heterodimer by CAN.
  • Fig. S12. Efficient targeting of CCL5-CXCL12 heterodimer by [VREY]4.
  • Fig. S13. Dose dependency of T cell chemotaxis elicited by single chemokines.
  • Fig. S14. Differential effects of chemokine combinations on T cell chemotaxis.
  • Fig. S15. Differential effects of chemokine heterodimerization on leukocyte recruitment.
  • Fig. S16. Microscopy of chemokine interactions at the cell surface.
  • Fig. S17. Mechanisms for synergy of chemokine heterodimers.
  • Fig. S18. Effect of heterodimers on signaling pathways, receptor affinity, and internalization.
  • Fig. S19. CCL5-CXCL4 heterodimers bind to heparin and prevent arrestin recruitment.
  • Fig. S20. Relevance of chemokine heterodimer formation in acute lung injury.
  • Fig. S21. Generation of mice deficient in Cxcl4 or Cxcl12 or carrying Cxcl4 variants.
  • Fig. S22. Analysis of atherosclerotic lesion in mice expressing Cxcl4 or its variant.
  • Fig. S23. Composition of aortic root lesions in mice expressing Cxcl4 or its variant.
  • Fig. S24. Obligate chemokine heterodimers mimic natural heterodimers.
  • Fig. S25. Summary scheme.
  • Table S1. Densitometry analysis of bidirectional immunoligand blotting.
  • Table S2. Kinetic analysis of chemokine binding by SPR.
  • Table S3. Weighted averaging of Δintensity changes and MDS-based in silico modeling.
  • Table S4. Sequence and origin of peptide inhibitors.
  • Table S5. CCL5-derived peptides specifically inhibit heterodimer formation.
  • Table S6. Lipid parameters and peripheral blood counts of different CXCL4 genotypes.
  • Table S7. Effect of OPRAH on lipid parameters and peripheral blood counts.
  • References (5363)

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