Quantification of cytokeratin 5 mRNA expression in the circulation of healthy human subjects and after lung transplantation.
BACKGROUND
Circulating epithelial progenitor cells are important for repair of the airway epithelium in a mouse model of tracheal transplantation. We therefore hypothesized that circulating epithelial progenitor cells would also be present in normal human subjects and could be important for repair of the airway after lung injury. As lung transplantation is associated with lung injury, which is severe early on and exacerbated during episodes of infection and rejection, we hypothesized that circulating epithelial progenitor cell levels could predict clinical outcome following lung transplantation.


RESULTS
Quantitative Real Time PCR was performed to determine peripheral blood mRNA levels of cytokeratin 5, a previously characterized marker of circulating epithelial progenitor cells. Cytokeratin 5 levels were evaluated in healthy human subjects, in lung transplant recipients immediately post-transplant and serially thereafter, and in heart transplant recipients. All normal human subjects examined expressed cytokeratin 5 in their buffy coat in amounts that were not significantly influenced by age or gender. There was a profound, statistically significant decrease in cytokeratin 5 mRNA expression levels in lung transplant patients compared to healthy human subjects (p = 3.1x10(-13)) and to heart transplant recipients. There was a moderate negative correlation between improved circulating cytokeratin 5 mRNA levels in lung transplant recipients with recovering lung function, as measured by improved FEV1 values (rho = -0.39).


CONCLUSIONS
Levels of cytokeratin 5 mRNA, a proxy marker for circulating epithelial progenitor cells, inversely correlated with disease status in lung transplant recipients. It may therefore serve as a biomarker of the clinical outcome of lung transplant patients and potentially other patients with airway injury.
Nickerson
Derek W
DW
Mattel Children's Hospital at UCLA, Division of Hematology Oncology, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America.
Presson
Angela P
AP
Weigt
Stephen S
SS
Gregson
Aric L
AL
Belperio
John A
JA
Gomperts
Brigitte N
BN
D000328:Adult; D000368:Aged; D017931:DNA Primers / Q000737:chemistry; D004847:Epithelial Cells / Q000166:cytology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D053555:Keratin-5 / Q000096:biosynthesis*; D055370:Lung Injury / Q000378:metabolism*; D016040:Lung Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology*
D017931:DNA Primers; D053555:Keratin-5; D012333:RNA, Messenger