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A role for fractalkine and its receptor (CX3CR1) in cardiac allograft rejection.

Publication ,  Journal Article
Robinson, LA; Nataraj, C; Thomas, DW; Howell, DN; Griffiths, R; Bautch, V; Patel, DD; Feng, L; Coffman, TM
Published in: J Immunol
December 1, 2000

The hallmark of acute allograft rejection is infiltration of the inflamed graft by circulating leukocytes. We studied the role of fractalkine (FKN) and its receptor, CX(3)CR1, in allograft rejection. FKN expression was negligible in nonrejecting cardiac isografts but was significantly enhanced in rejecting allografts. At early time points, FKN expression was particularly prominent on vascular tissues and endothelium. As rejection progressed, FKN expression was further increased, with prominent anti-FKN staining seen around vessels and on cardiac myocytes. To determine the capacity of FKN on endothelial cells to promote leukocyte adhesion, we performed adhesion assays with PBMC and monolayers of TNF-alpha-activated murine endothelial cells under low-shear conditions. Treatment with either anti-FKN or anti-CX(3)CR1-blocking Ab significantly inhibited PBMC binding, indicating that a large proportion of leukocyte binding to murine endothelium occurs via the FKN and CX(3)CR1 adhesion receptors. To determine the functional significance of FKN in rejection, we treated cardiac allograft recipients with daily injections of anti-CX(3)CR1 Ab. Treatment with the anti-CX(3)CR1 Ab significantly prolonged allograft survival from 7 +/- 1 to 49 +/- 30 days (p < 0.0008). These studies identify a critical role for FKN in the pathogenesis of acute rejection and suggest that FKN may be a useful therapeutic target in rejection.

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Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

December 1, 2000

Volume

165

Issue

11

Start / End Page

6067 / 6072

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transplantation, Homologous
  • Receptors, Chemokine
  • Receptors, CXCR3
  • Mice, Transgenic
  • Mice, Inbred DBA
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Membrane Proteins
 

Citation

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Robinson, L. A., Nataraj, C., Thomas, D. W., Howell, D. N., Griffiths, R., Bautch, V., … Coffman, T. M. (2000). A role for fractalkine and its receptor (CX3CR1) in cardiac allograft rejection. J Immunol, 165(11), 6067–6072. https://doi.org/10.4049/jimmunol.165.11.6067
Robinson, L. A., C. Nataraj, D. W. Thomas, D. N. Howell, R. Griffiths, V. Bautch, D. D. Patel, L. Feng, and T. M. Coffman. “A role for fractalkine and its receptor (CX3CR1) in cardiac allograft rejection.J Immunol 165, no. 11 (December 1, 2000): 6067–72. https://doi.org/10.4049/jimmunol.165.11.6067.
Robinson LA, Nataraj C, Thomas DW, Howell DN, Griffiths R, Bautch V, et al. A role for fractalkine and its receptor (CX3CR1) in cardiac allograft rejection. J Immunol. 2000 Dec 1;165(11):6067–72.
Robinson, L. A., et al. “A role for fractalkine and its receptor (CX3CR1) in cardiac allograft rejection.J Immunol, vol. 165, no. 11, Dec. 2000, pp. 6067–72. Pubmed, doi:10.4049/jimmunol.165.11.6067.
Robinson LA, Nataraj C, Thomas DW, Howell DN, Griffiths R, Bautch V, Patel DD, Feng L, Coffman TM. A role for fractalkine and its receptor (CX3CR1) in cardiac allograft rejection. J Immunol. 2000 Dec 1;165(11):6067–6072.

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

December 1, 2000

Volume

165

Issue

11

Start / End Page

6067 / 6072

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transplantation, Homologous
  • Receptors, Chemokine
  • Receptors, CXCR3
  • Mice, Transgenic
  • Mice, Inbred DBA
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Membrane Proteins