Upregulation of T-helper 1 cytokines and chemokine expression in post- transplant airway obliteration

Annette Boehler, Hui Bai Xiao, Mingyao Liu, Stephen Cassivi, Dean Chamberlain, Arthur S. Slutsky, Shaf Keshavjee

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

The major obstacle to long-term survival after lung transplantation is chronic graft dysfunction manifest as bronchiolitis obliterans. Since the early stages are characterized by proliferation of itinerant cells (lymphocytes and macrophages), we hypothesized that cytokines and chemokines may play a role in the development of the fibroproliferative process. In a heterotopic rat tracheal transplant model, we studied isografts and allografts 3, 7, and 21 d after transplantation as representative time points for the triphasic time course in the evolution of allograft airway obliteration. Using a semiquantitative RT-PCR technique, intragraft gene expression of T-helper 1 (Th1)- and Th2-type cytokines and of C-C and C-X-C chemokines was examined. The results of our study show a distinct pattern of cytokine and chemokine gene expression in the development of post-transplant airway obliteration. Allografts, in contrast to isografts, showed a strong and persistent Th1-type response (expression of interleukin-2 and interferon- γ genes), even after fibrous airway obliteration was complete, suggesting an ongoing allo-immune process until late in the fibroproliferative stage. RANTES and MCP-1 were also upregulated late after transplantation, whereas MIP-2 upregulation occurred early post-transplant and was not restricted to allografts alone, which might reflect alloantigen-independent processes after transplantation that are present in both allografts and isografts.

Original languageEnglish (US)
Pages (from-to)1910-1917
Number of pages8
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume159
Issue number6
StatePublished - 1999
Externally publishedYes

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Chemokines
Allografts
Isografts
Up-Regulation
Cytokines
Transplants
Transplantation
Bronchiolitis Obliterans
Gene Expression
CXC Chemokines
Chemokine CCL5
Isoantigens
Lung Transplantation
Interferons
Interleukin-2
Macrophages
Cell Proliferation
Lymphocytes
Polymerase Chain Reaction
Genes

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Boehler, A., Xiao, H. B., Liu, M., Cassivi, S., Chamberlain, D., Slutsky, A. S., & Keshavjee, S. (1999). Upregulation of T-helper 1 cytokines and chemokine expression in post- transplant airway obliteration. American Journal of Respiratory and Critical Care Medicine, 159(6), 1910-1917.

Upregulation of T-helper 1 cytokines and chemokine expression in post- transplant airway obliteration. / Boehler, Annette; Xiao, Hui Bai; Liu, Mingyao; Cassivi, Stephen; Chamberlain, Dean; Slutsky, Arthur S.; Keshavjee, Shaf.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 159, No. 6, 1999, p. 1910-1917.

Research output: Contribution to journalArticle

Boehler, A, Xiao, HB, Liu, M, Cassivi, S, Chamberlain, D, Slutsky, AS & Keshavjee, S 1999, 'Upregulation of T-helper 1 cytokines and chemokine expression in post- transplant airway obliteration', American Journal of Respiratory and Critical Care Medicine, vol. 159, no. 6, pp. 1910-1917.
Boehler, Annette ; Xiao, Hui Bai ; Liu, Mingyao ; Cassivi, Stephen ; Chamberlain, Dean ; Slutsky, Arthur S. ; Keshavjee, Shaf. / Upregulation of T-helper 1 cytokines and chemokine expression in post- transplant airway obliteration. In: American Journal of Respiratory and Critical Care Medicine. 1999 ; Vol. 159, No. 6. pp. 1910-1917.
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