Cytolytic human lung lymphocytes: characterization of intragranular protease content and response to interleukin-2.
Cytolytic lymphocytes play an important role in defense against viral and neoplastic disease. Integral to the function of these cells is the content of lysosomal granules. Recent attention has focused on a family of proteases present in the granules of natural killer (NK) cells, interleukin-2 (IL-2)-activated NK cells (LAK cells), and cytotoxic T lymphocytes (CTL). In the current investigation, lymphocytes were obtained from human lung parenchyma and peripheral blood. Following activation with IL-2, both groups of lymphocytes exhibited comparable cytolytic activity against K562 targets. Lysosomal granules obtained from these cells contained two serine proteases with molecular weights of 30 and 28 kD. These proteases were capable of hydrolyzing benzyloxycarbonyl-L-lysine thiobenzyl ester (BLT-ester), a substrate of cytolytic lymphocyte proteases. When compared to blood, unactivated lung lymphocytes contained significantly higher levels of protease content. Although IL-2 produced a significant increase in blood lymphocyte protease content, no change in lung lymphocyte granule protease activity was observed. We conclude that cytolytic lung lymphocytes contain high levels of lysosomal granule protease but differ from blood lymphocytes in the ability to increase protease content following activation with IL-2. The high level of protease content in cytolytic lung lymphocytes suggests that these cells could produce local tissue injury during the release of lysosomal granules.
Breite
W M
WM
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-9034.
Dal Nogare
A R
AR
Yarbrough
W C
WC
Weissler
J C
JC
D003594:Cytoplasmic Granules / Q000201:enzymology*; D010450:Endopeptidases / Q000378:metabolism*; D053804:Granzymes; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000201:enzymology* / Q000502:physiology / Q000648:ultrastructure; D007694:Killer Cells, Natural / Q000201:enzymology* / Q000502:physiology / Q000648:ultrastructure; D008168:Lung / Q000166:cytology*; D008213:Lymphocyte Activation; D008247:Lysosomes / Q000201:enzymology; D008970:Molecular Weight; D012697:Serine Endopeptidases / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology* / Q000502:physiology / Q000648:ultrastructure
D007376:Interleukin-2; D010450:Endopeptidases; D053804:Granzymes; D012697:Serine Endopeptidases; C509212:GZMA protein, human