ALPHA-1-ANTITRYPSIN P-LOWELL - A NORMALLY FUNCTIONING VARIANT PRESENTIN LOW CONCENTRATION

Background: Alpha-1-antitrypsin deficiency is associated with a high r isk for the development of emphysema, particularly for phenotype Pi ZZ , which is both deficient and an abnormal inhibitor of the powerful pr oteolytic enzyme, human neutrophil elastase. The rare variant P-Lowell is also expressed at abnormally low levels, but its anti-elastase act ivity has not been described. Aim: To study the anti-elastase activity of alpha-1-antitrypsin P-Lowell and compare it to the common M, S and Z proteins. Method: Alpha-1-antitrypsin from a female patient aged 75 years with the rare genotype P-Lowell Null(Bellingham) was studied fo r its ability to inhibit human neutrophil elastase in a time dependent manner. Results: P-Lowell has near normal function as an inhibitor of human neutrophil elastase with an association rate constant of 7.4 x 10(6) M(-1)s(-1) at 25 degrees C, similar to that of M and S. Conclusi on: Alpha-1-antitrypsin P-Lowell is associated with a severe deficienc y of alpha-1-antitrypsin similar to Z, but unlike that protein It has near normal function as an anti-elastase.