INCREASED GELATINOLYTIC ACTIVITY IN BRONCHOALVEOLAR LAVAGE FLUID IN STABLE LUNG-TRANSPLANT RECIPIENTS

Proteolytic enzymes have been proposed to play a role in the pathogene sis of various inflammatory pulmonary diseases accompanied by parenchy mal remodeling. To assess the role of inflammatory cells and proteolyt ic enzymes in the development of chronic allograft rejection after lun g transplantation, bronchoalveolar ravage fluid (BALF) samples from cl inically stable lung transplant (LT) recipients (i.e., without evidenc e of active infection or rejection), heart transplant (HT) recipients, and healthy volunteers (NL) were analyzed for total white blood cell (WBC) count and differential cell count, along with gelatinolytic/type IV collagenolytic activity. The LT group displayed a significantly in creased total WBC count, neutrophil count, and percent neutrophils com pared with the NL group, confirming the presence of inflammation. Furt hermore, gelatin zymography revealed a significant increase in activit y of the 72 and 92 kD gelatinases in the LT group compared with the NL group. A positive correlation existed between neutrophil counts and t he increase in proteolytic activity. Immunosuppressive therapy did not account for the findings, since no significant difference in cell cou nts or proteolytic activity existed between the NL and HT control grou ps. These findings, together with those of others that relate chronic lung allograft dysfunction to an increase in BALF neutrophils and coll agen matrix remodeling, collectively indicate that up-regulated proteo lytic activity may have a role in chronic rejection after lung transpl antation.