Our results suggest that the origin of CK5 expressing cells in circulation may be from the bone marrow, the thymus, or may be derived from the lung tissue itself, or may be derived from all of these compartments. If the origin of the circulating epithelial progenitor cells is the bone marrow then it is possible that the immunosuppression that the lung transplant patients are on could be responsible for the decrease in the expression of CK5. We therefore analyzed the expression of CK5 in the circulation of heart transplant patients who are also on immunosuppression but do not have any major airway epithelial injury. We found a significant difference between the amount of Cefuroxime axetil circulating epithelial progenitor cells in heart transplant patients and lung transplant patients, which suggests that circulating epithelial progenitor cells are specific for airway repair. We also found a trend towards heart transplant patients having less circulating epithelial progenitor cells than normal human subjects. The heart transplant group were on lower doses of immunosuppression than the lung transplant patients, which suggests that immunosuppression may be playing a role in the reduction of circulating epithelial progenitor cells found in transplant patients. It is also possible that the differences in CK5 expression in circulation may result from changes in vascular permeability or altered blood supply to the lung allografts. We did not find a difference in CK5 mRNA expression in normal human subjects with increasing age and this might be expected as normal repair and regeneration decreases with age. However, there are likely many variables in addition to age that contribute to overall repair of the airway. CK5 expressing cells are also found as basal cells in other complicated epithelia, most notably skin and prostate. We would therefore have predicted that gender differences might be seen,Cefcapene Pivoxil Hydrochloride although this was not the case in our control samples. However, as benign prostatic hypertrophy is associated with advancing age, it will be important in the future to examine CK5 levels in older normal human subjects to determine if there is a gender difference in this group. Previous studies on the engraftment of bone marrow-derived epithelial cells in the distal airway after lung injury have shown conflicting results. Our results demonstrated that circulating epithelial cells are present in the circulation of all normal human subjects examined. However, flow cytometry analysis of CK5 expressing cells in circulation are required to confirm this. Our experiments were performed retrospectively on frozen RNA samples and therefore flow cytometry for CK5 could not be performed. Our studies were not designed to assess the magnitude of engraftment of the circulating epithelial cells in the airway. However, the statistically significant difference between lung transplant patients and normal human subjects with regard to their CK5 mRNA levels suggested that circulating epithelial cells may be important in normal airway repair. In addition, the correlation of the increase in CK5 levels with the improvement in pulmonary function testing post-transplantation suggests that CK5 mRNA levels in circulation could be used as a biomarker of airway repair.