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Chemokines have diverse abilities to form solid phase gradients.

Publication ,  Journal Article
Patel, DD; Koopmann, W; Imai, T; Whichard, LP; Yoshie, O; Krangel, MS
Published in: Clin Immunol
April 2001

Chemokines play critical roles in leukocyte recruitment into sites of inflammation such as rheumatoid arthritis (RA). While chemokines immobilized on endothelium (solid-phase), but not soluble chemokines, direct rolling leukocytes to firmly adhere to endothelium, soluble and solid-phase chemokine gradients may play important roles in leukocyte extravasation into the tissue. In this study, we have sought to determine (1) if chemokines can be immobilized on structures in the extravascular space, (2) the mechanisms by which chemokines may be immobilized, and (3) if different chemokines have similar potentials to form solid-phase gradients. While secreted alkaline phosphatase (SEAP)-tagged chemokines SLC (CCL21), TARC (CCL17), and RANTES (CCL5) bound to mast cells and the extracellular matrix (ECM) in RA synovium under physiologic salt conditions, MCP1 (CCL2), MIP1 alpha (CCL3), MIP1 beta (CCL4), and fractalkine (FKN, CX3CL1) fusion proteins did not detectably bind. Chemokine binding to ECM and mast cells in situ and to immobilized heparin was inhibited by high salt and glycosaminoglycans (GAGs) heparin, heparan sulfate, chondroitin sulfate, and dermatan sulfate, but not by dextran or hyaluronan, indicating that the chemokines bind to highly sulfated GAGs. Chemokine binding to synovial structures correlated strongly with avidity of chemokine binding to heparin (SLC > TARC > RANTES > MIP1 beta > MCP1 > MIP1 alpha > FKN). A RANTES mutant with decreased avidity for heparin was not able to bind to ECM or mast cells. Thus, these data indicate that chemokines can bind to ECM and mast cell granule constituents in situ via interactions with GAGs. Further, only a subset of chemokines were able to bind efficiently to structures in the extravascular space, indicating that chemokines may form different types of gradients based on their GAG binding ability and that chemotactic gradients in tissues may be quite complex.

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Published In

Clin Immunol

DOI

ISSN

1521-6616

Publication Date

April 2001

Volume

99

Issue

1

Start / End Page

43 / 52

Location

United States

Related Subject Headings

  • Synovial Membrane
  • Recombinant Fusion Proteins
  • Mast Cells
  • Immunology
  • Humans
  • Heparin
  • Extracellular Matrix
  • Chemokines
  • Arthritis, Rheumatoid
  • Alkaline Phosphatase
 

Citation

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Patel, D. D., Koopmann, W., Imai, T., Whichard, L. P., Yoshie, O., & Krangel, M. S. (2001). Chemokines have diverse abilities to form solid phase gradients. Clin Immunol, 99(1), 43–52. https://doi.org/10.1006/clim.2000.4997
Patel, D. D., W. Koopmann, T. Imai, L. P. Whichard, O. Yoshie, and M. S. Krangel. “Chemokines have diverse abilities to form solid phase gradients.Clin Immunol 99, no. 1 (April 2001): 43–52. https://doi.org/10.1006/clim.2000.4997.
Patel DD, Koopmann W, Imai T, Whichard LP, Yoshie O, Krangel MS. Chemokines have diverse abilities to form solid phase gradients. Clin Immunol. 2001 Apr;99(1):43–52.
Patel, D. D., et al. “Chemokines have diverse abilities to form solid phase gradients.Clin Immunol, vol. 99, no. 1, Apr. 2001, pp. 43–52. Pubmed, doi:10.1006/clim.2000.4997.
Patel DD, Koopmann W, Imai T, Whichard LP, Yoshie O, Krangel MS. Chemokines have diverse abilities to form solid phase gradients. Clin Immunol. 2001 Apr;99(1):43–52.
Journal cover image

Published In

Clin Immunol

DOI

ISSN

1521-6616

Publication Date

April 2001

Volume

99

Issue

1

Start / End Page

43 / 52

Location

United States

Related Subject Headings

  • Synovial Membrane
  • Recombinant Fusion Proteins
  • Mast Cells
  • Immunology
  • Humans
  • Heparin
  • Extracellular Matrix
  • Chemokines
  • Arthritis, Rheumatoid
  • Alkaline Phosphatase