Altered levels of CC chemokines during pulmonary CMV predict BOS and mortality post-lung transplantation.

Abstract

Pulmonary CMV infection (CMVI) and disease (CMVD) is associated with reduced long-term survival post-lung transplantation, however, the specific biologic mechanisms remain unclear. We have demonstrated a role of CC chemokines during lung allograft dysfunction. Based on these findings, we hypothesized that pulmonary CMV upregulates the expression of multiple CC chemokines that leads to allograft dysfunction and decreased long-term survival. We performed a nested case control study in lung transplant recipients to investigate alterations in CC chemokine biology during pulmonary CMV. Levels of CC chemokines were measured in bronchoalveolar lavage fluid (BALF) from recipients with CMVI (n = 33), CMVD (n = 6), and in healthy lung transplant controls (n = 33). We found a trend toward increased levels of MIP-1alpha/CCL3 during pulmonary CMVI. Levels of MCP-1/CCL2 and RANTES/CCL5 were significantly elevated during pulmonary CMV. Interestingly, elevated levels of CCL3 in BALF were protective with regards to survival. Importantly, elevated levels of CCL2 in BALF predicted the development of BOS, while elevated levels of CCL5 in BALF predicted an increase in mortality post-lung transplant. Altered levels of specific CC chemokines during pulmonary CMV are associated with future clinical outcomes. These results suggest a possible utility of BALF CC chemokines as biomarkers for guiding risk assessment during pulmonary CMV post-lung transplantation.

• Authors: S S Weigt, R M Elashoff, M P Keane, R M Strieter, B N Gomperts, Y Y Xue, A Ardehali, A L Gregson, B Kubak, M C Fishbein, R Saggar, D J Ross, J P Lynch 3rd, D A Zisman, J A Belperio
• Journal: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons (Am J Transplant) Vol. 8 Issue 7 Pg. 1512-22 (Jul 2008) ISSN: 1600-6143 [Electronic] United States
• PMID: 18513272 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• CCL2 protein, human
• CCL3 protein, human
• Chemokine CCL2
• Chemokine CCL3
• Chemokines, CC
• Receptors, Chemokine
• macrophage inflammatory protein 1alpha receptor

Topics

• Bronchiolitis Obliterans (blood, mortality, virology)
• Bronchoalveolar Lavage Fluid (virology)
• Case-Control Studies
• Chemokine CCL2 (blood)
• Chemokine CCL3 (blood)
• Chemokines, CC (blood)
• Cytomegalovirus Infections (blood, mortality)
• Female
• Graft Survival
• Humans
• Lung Transplantation (mortality)
• Male
• Middle Aged
• Receptors, Chemokine (blood)
• Risk Assessment
• Up-Regulation