Studies on the mechanism of antibody-dependent polymorphonuclear leukocyte-mediated cytotoxicity

R. A. Clark, S. J. Klebanoff

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

A well characterized Moloney virus-induced mouse ascitic lymphoma line of BALB/c origin has been designated LSTRA. Human polymorphonuclear leukocytes (PMN) were cytotoxic to LSTRA cells in the presence of anti-LSTRA serum as determined by a 51Cr release assay. Cytotoxicity was observed with effector to target cell ratios as low as 0.25:1 and with incubation periods as short as 30 min. Under the conditons employed, human blood mononuclear cells had only minimal cytotoxic activity. Immunologic specificity was demonstrated by the loss of activity when immune serum was preabsorbed with target cells or replaced with normal (preimmune) serum and the lack of by 51Cr release from an unrelated target cell. Viable PMN were required as demonstrated by the loss of cytotoxicity on heating or homogenization. Further, an intact PMN metabolic burst was essential for maximal activity since PMN from patients with chronic granulomatous disease were only minimally active. The myeloperoxidase-H2O2-halide system of the PMN was not responsible for cytotoxicity since activity was normal with myeloperoxidase deficient PMN, was preserved in the presence of azide, cyanide or catalase, and was only slightly dependent on halides. Lack of inhibition by heparin militated against a role for PMN granular cationic proteins. Cytotoxicity was blocked by inhibitors of glycolysis, but not by an inhibitor of oxidative phosphorylation. The use of chelating agents indicated a requirement for divalent cations, primarily Mg++. Inhibition of cytotoxicity by the anti-tubulins, colchicine, and vincristine, suggested a role for microtubules. These studies suggest that antibody-dependent PMN-mediated tumor cell cytotoxicity requires specific antibody, viable PMN, a burst of PMN oxidative metabolism, glycolysis, divalent cations, and microtubular function. The PMN lysosomal constituents, myeloperoxidase and the cationic proteins, did not appear to be involved under the conditions employed.

Original languageEnglish (US)
Pages (from-to)1413-1418
Number of pages6
JournalJournal of Immunology
Volume119
Issue number4
StatePublished - Dec 1 1977
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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