Abstract: The invention describes catabolism of A&bgr; by endothelin converting enzymes (ECEs). Methods of identifying compounds that upregulate ECEs are provided by the invention. Further provided by the invention are methods of regulating A&bgr; catabolism in a cell and methods of decreasing the amount of A&bgr; in a cell. The invention discloses methods of diagnosing an individual with AD and methods of treating such an individual. The invention further discloses methods of identifying compounds that have anti-hypertension activity but do not cause an increase in the level of A&bgr;. Further, the invention provides mutant ECE nucleic acids and mutant ECE polypeptides.

Abstract: The invention describes catabolism of A&bgr; by endothelin converting enzymes (ECEs). Methods of identifying compounds that upregulate ECEs are provided by the invention. Further provided by the invention are methods of regulating A&bgr; catabolism in a cell and methods of decreasing the amount of A&bgr; in a cell. The invention discloses methods of diagnosing an individual with AD and methods of treating such an individual. The invention further discloses methods of identifying compounds that have anti-hypertension activity but do not cause an increase in the level of A&bgr;. Further, the invention provides mutant ECE nucleic acids and mutant ECE polypeptides.

Abstract: A protein conjugate consisting of antibody directed at the pIgR and A1AT can be transported specifically from the basolateral surface of epithelial cells to the apical surface. This approach provides us with the ability to deliver a therapeutic protein directly to the apical surface of the epithelium, by targeting the pIgR with an appropriate ligand. Thus, the highest concentration of the antiprotease will be at the apical surface, where it can do the greatest good in accelerating the inflammatory response.

Abstract: A bifunctional molecule consisting of a therapeutic molecule and a ligand which specifically binds a transcytotic receptor can be transported specifically from the basolateral surface of epithelial cells to the apical surface. This approach provides the ability to deliver a therapeutic molecule directly to the apical surface of the epithelium, by targeting the transcytotic receptor with an appropriate ligand. Thus, the highest concentration of the therapeutic molecule will be at the apical surface, where it can have the greatest therapeutic effect.

Abstract: A protein conjugate consisting of antibody directed at the pIgR and A.sub.1 AT can be transported specifically from the basolateral surface of epithelial cells to the apical surface. This approach provides us with the ability to deliver a therapeutic protein directly to the apical surface of the epithelium, by targeting the pIgR with an appropriate ligand. Thus, the highest concentration of the antiprotease will be at the apical surface, where it can do the greatest good in accelerating the inflammatory response.