Production of plasminogen activator by human natural killer cells. Large granular lymphocytes.

Abstract

Highly purified populations of natural killer (NK) cells: large granular lymphocytes (LGL) were used to demonstrate that freshly isolated and interleukin 2-cultured LGL produce the specific neutral serine protease, plasminogen activator (PA). The enzyme is expressed in both an extracellular form as well as in a cell-associated form. Upon subcellular distribution the latter form of the enzyme is associated with a cell-surface membrane-enriched fraction. LGL PA exists in multiple MW forms ranging from 100,000 to 26,000. Interferon (IFN), the major positive regulator of NK cytolytic activity, caused a substantial enhancement of cell-associated, but not extracellular, PA. In contrast, LGL isolated from patients with Chediak-Higashi syndrome, who are known to be defective in NK activity, displayed low PA activity, altered morphology and low NK killing relative to LGL isolated from nomal donors. The possible role of LGL PA in the lysis of tumor cells by NK cells, either directly or indirectly, is discussed.