HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Edward D. Verrier Michael S. Mulligan Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Naidu, B. V. Articles by Mulligan, M. S. Search for Related Content PubMed PubMed Citation Articles by Naidu, B. V. Articles by Mulligan, M. S. Related Collections Lung - transplantation

Ann Thorac Surg 2003;75:1118-1122
© 2003 The Society of Thoracic Surgeons

---

Original article: general thoracic

Broad-spectrum chemokine inhibition ameliorates experimental obliterative bronchiolitis

^a Division of Cardiothoracic Surgery, Department of Surgery, University of Washington, Seattle, Washington, USA
^b Department of Medicine, University of Cambridge, Addenbrooke Hospital, Cambridge, United Kingdom

Accepted for publication November 6, 2002.

^* Address reprint requests to Dr Mulligan, Box 356310, University of Washington, 1959 NE Pacific St, Seattle, WA 98195, USA
e-mail: msmmd{at}u.washington.edu

BACKGROUND: Obliterative bronchiolitis (OB) affects over half of all long-term survivors after lung transplantation. Respiratory epithelial cell injury, peribronchial inflammation, and proliferation of fibrovascular connective tissue causing airway occlusion characterize this lesion. Several chemokines participate in experimental OB, and singular blockade is only partially effective. We hypothesized that a broad-spectrum chemokine inhibitor would be an effective intervention in preventing the progression of OB in an established heterotopic tracheal transplantation model.

METHODS: Tracheas from Brown-Norway or Lewis rats were transplanted subcutaneously into Lewis recipients. Treated, allogeneic recipients received either a broad-spectrum chemokine inhibitor in its active (NR58.3.14.3) or inactive (NR58.3.14.4) form at a dose of 30 mg/kg daily. Luminal obstruction, epithelial loss, leukocytic infiltrates, and inflammatory cytokine mRNA levels were assessed in explanted tracheal samples 14 days after transplantation.

RESULTS: After 14 days, allografts receiving the inactive chemokine inhibitor demonstrated marked peribronchial inflammation, near complete loss of respiratory epithelium, and extensive intraluminal proliferation of fibrovascular connective tissue, with a mean 84% ± 5% reduction in airway lumen cross-sectional area. Isografts showed limited inflammation, with minimal loss of epithelium and luminal occlusion. Allogeneic recipients treated with the active chemokine inhibitor showed a significant preservation of respiratory epithelium, minimal peribronchial inflammation, and a marked decrease in the loss of airway cross-sectional area (23% ± 1%) (p < 0.001).

CONCLUSIONS: These findings further characterize the participation of chemokines in OB, and suggest that broad-spectrum chemokine inhibition may potentially be a useful therapeutic tool in slowing the progression of this disease.

This article has been cited by other articles:

				U. A. Kayisli, M. Berkkanoglu, Lufang Zhang, G. Kizilay, and A. Arici The Broad-Spectrum Chemokine Inhibitor NR58-3.14.3 Suppresses the Implantation and Survival of Human Endometrial Implants in the Nude Mice Endometriosis Model Reproductive Sciences, December 1, 2007; 14(8): 825 - 835. [Abstract] [PDF]

				M. Berkkanoglu, L. Zhang, M. Ulukus, H. Cakmak, U. A. Kayisli, S. Kursun, and A. Arici Inhibition of chemokines prevents intraperitoneal adhesions in mice Hum. Reprod., November 1, 2005; 20(11): 3047 - 3052. [Abstract] [Full Text] [PDF]