The elimination of secretory leukocyte protease inhibitor (SLPI) after intravenous injection in dog and man

Abstract

After an intravenous injection of ³⁵Sulphur-labelled secretory leukocyte protease inhibitor (SLPI) in four dogs, there was a rapid initial clearance (half-life 10 min) of radioactivity and immunoreactive SLPI from plasma. Later, the immunoreactive SLPI cleared more rapidly (T_1/2 = 60 min) than the radioactivity, indicating the gradual appearance of radioactive degradation products. Intact recombinant human SLPI as well as radioactive fragments appeared in the urine. The urinary excretion of radioactivity during the first 3 h was less than 10% of the injected dose. After killing at 3 h, the kidneys contained more radioactivity per gram tissue than the other parenchymatous organs.

Following an intravenous injection of ^l25Iodine-labelled native SLPI in three human volunteers, a rapid initial clearance of both protein-bound and total plasma radioactivity (half-life 10 min) was seen. Later, the protein-bound radioactivity cleared slower (half-life 120 min) than the total radioactivity, indicating a progressive degradation of SLPI with release of radioactive fragments to plasma. After 54 h 80-96% of the radioactivity had been excreted in the urine, mainly as free ^l25Iodine. No intact SLPI was found in the urine. A renal metabolism of SLPI is assumed, which is supported also by the finding of elevated serum levels of SLPI in uraemic patients. The possible therapeutic use of SLPI is briefly discussed.

Key Words:

• leukocyte
• Protease
• protease inhibitor