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°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 β-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.

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