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In vitro tumor cell cytolysis mediated by peptide defensins of human and
rabbit granulocytes
A Lichtenstein, T Ganz, ME Selsted and RI Lehrer
We examined the activity of defensins, cysteine-rich cationic peptides that
are abundant in the cytoplasmic granules of human and rabbit granulocytes,
against various tumor targets. The three human defensins, HNP-1, HNP-2, and
HNP-3, lysed human and murine targets in chromium release and dye exclusion
assays. Defensin-mediated tumor cell lysis was concentration-dependent,
inhibited by serum, and dependent on temperature-sensitive events. Lysis
was first detected by three hours of incubation and it reached a plateau
between eight and 14 hours. In vitro exposure of murine teratocarcinoma
cells to HNP 1-3 abrogated their oncogenicity in vivo. Nonmalignant target
cells were also susceptible to defensin-mediated lysis. Four rabbit
granulocyte defensins exerted marked (NP-1, NP-2) or moderate (NP-3a,
NP-3b) cytotoxic activity, whereas defensin NP-5 was not cytotoxic. When
tumor cells were incubated with human defensins in combination with
hydrogen peroxide, synergistic cytotoxicity was detected. As defensins are
released from granulocytes by various stimuli, their release could
contribute to extracellular cytotoxicity which is independent of reactive
oxygen intermediates.
Volume 68,
Issue 6,
pp. 1407-1410,
12/01/1986
Copyright © 1986 by The American Society of Hematology
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