Upregulation of chemokines in bronchoalveolar lavage fluid as a predictive marker of post-transplant airway obliteration.
BACKGROUND
The early stage of post-transplant obliterative bronchiolitis (OB) is characterized by an influx of inflammatory cells to the lung, among which neutrophils may play a role in key events. The potential for chemokines to induce leukocyte accumulation in the alveolar space was investigated. We assessed whether changes in the chemotactic expression profile could be used as sensitive markers of the onset of OB.


METHODS
Serial bronchoalveolar lavage (BAL) fluids from 13 stable healthy recipients and 8 patients who developed bronchiolitis obliterans syndrome (BOS) were analyzed longitudinally for concentrations of interleukin-8 (IL-8), chemokines regulated-upon-activation and normal T-cell expressed and secreted (RANTES) and monocyte chemoattractant protein-1 (MCP-1), soluble intracellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). These were assessed by enzyme-linked immunosorbent assay (ELISA).


RESULTS
Significantly elevated percentages of BAL neutrophils and IL-8 levels were found at the pre-clinical stage of BOS, on average 151 +/- 164 days and 307 +/- 266 days, respectively, before diagnosis of BOS. There was also early upregulation of RANTES and MCP-1 in the BOS group (mean 253 +/- 323 and 152 +/- 80 days, respectively, before diagnosis of BOS). The level of MCP-1 was consistently higher than that of RANTES until airway obliteration. BAL sICAM-1 and sVCAM-1 levels were not statistically different between the groups.


CONCLUSIONS
These data support the belief that RANTES, IL-8 and MCP-1 play a crucial role in the pathogenesis of OB. The results show that relevant increased levels of such chemokines may predict BOS, and suggest that there is potential for some of these markers to be used as early and sensitive markers of the onset of BOS. Longitudinal monitoring of these chemokine signals may contribute to better management of patients at risk for developing OB, at a stage when remodeling can either be reversed or altered.
Reynaud-Gaubert
Martine
M
Division of Chirurgie Thoracique, UPRES 3287, Hôpital Sainte Marguerite, Marseille, France. mreynaud@ap-hm.fr
Marin
Valerie
V
Thirion
Xavier
X
Farnarier
Catherine
C
Thomas
Pascal
P
Badier
Monique
M
Bongrand
Pierre
P
Giudicelli
Roger
R
Fuentes
Pierre
P
D015415:Biomarkers / Q000032:analysis; D001989:Bronchiolitis Obliterans / Q000175:diagnosis* / Q000209:etiology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000166:cytology; D018932:Chemokine CCL2 / Q000032:analysis*; D018946:Chemokine CCL5 / Q000032:analysis*; D015331:Cohort Studies; D005500:Follow-Up Studies; D016027:Heart Transplantation; D006801:Humans; D016209:Interleukin-8 / Q000032:analysis*; D016040:Lung Transplantation; D018375:Neutrophil Activation; D011183:Postoperative Complications / Q000175:diagnosis* / Q000209:etiology; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012306:Risk; D013577:Syndrome; D015854:Up-Regulation
D015415:Biomarkers; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D016209:Interleukin-8