Inhibition of human neutrophil elastase activity by encapsulated serum (Serumsome) therapy

Abstract

In order to inhibit human leukocyte proteolytic activity as a means of arresting the inflammatory response in tissues in vivo, we have designed a novel antiprotease carrier named serumsomes. Stabilized human serum was added to a flask containing a film of dried, purified lipids (phosphatidylcholine/dicetyl phosphate/cholesterol, 70:20:10) and hand-shaken for 10 min. Equal volumes of human neutrophils, and either serumsomes (in stabilized human serum) or stabilized human serum alone were mixed together. Following 2 h of incubation at 37 degrees C, the total elastase content of the neutrophils was reduced to 60 +/- 15% and 83 +/- 7% of the original activity by serumsomes and stabilized human serum, respectively. Analysis of beta-glucuronidase activity, a nonproteolytic lysosomal marker enzyme, revealed no diminution of activity during either of these incubations. These experiments demonstrate that human neutrophils are capable of interacting with serumsomes in vitro, selectively inhibiting the lysosomal protease elastase. By administering serumsomes in vivo, one may potentially preload blood leukocytes with serum antiproteases prior to their migration to inflammatory sites and thus possibly reduce the extent of tissue injury.