Faculty Collaboration Database

Induction of porcine granulocyte-mediated tumor cytotoxicity by two distinct monoclonal antibodies against lytic trigger molecules (PNK-E/G7). J Immunol 1993 Dec 15;151(12):7117-27

Date

12/15/1993

Pubmed ID

8258715

Scopus ID

2-s2.0-0027140285 (requires institutional sign-in at Scopus site)   16 Citations

Abstract

PNK-E and G7 mAb bind to distinct porcine granulocyte function-associated molecules and induce granulocyte-mediated cytotoxicity against tumor targets. PNK-E mAb binds to a 205-kDa molecule that reduces to a dispersed band of 50 kDa on SDS-PAGE analysis. Previous work demonstrates that G7 mAb immunoprecipitates a molecule that appears as a heterodispersed 40-kDa band under both reducing and nonreducing conditions on SDS-PAGE analysis. Whole but not F(ab')2 PNK-E and G7 mAb induce dose-dependent porcine granulocyte-mediated lysis of FcR+ but not FcR- targets, suggesting a redirected cytotoxicity mechanism of granulocyte-mediated killing. Fresh porcine granulocytes also mediate significant levels of antibody-dependent cellular cytotoxicity (ADCC) against nucleated (SB) target cells. Neither whole nor F(ab')2 PNK-E mAb affects granulocyte-mediated ADCC against SB target cells. However, both whole and F(ab')2 G7 mAb inhibit granulocyte-mediated ADCC against SB targets by approximately 50%. Bound F(ab')2 G7 mAb inhibits PNK-E mAb-induced granulocyte-mediated cytotoxicity against K562 targets, but bound F(ab')2 PNK-E mAb does not inhibit G7 mAb-induced granulocyte-mediated cytotoxicity, suggesting a physical association between the PNK-E and G7 molecules on the surface of porcine granulocytes. PNK-E and G7 hybridoma cells are readily lysed by granulocyte effectors, further supporting that the PNK-E and G7 molecules are cytolytic trigger molecules on granulocytes. These data demonstrate that PNK-E and G7 mAb bind to distinct granulocyte lytic trigger molecules and induce potent granulocyte-mediated cytotoxicity against nucleated tumor targets through a mechanism of redirected cytotoxicity.

Author List

Wierda WG, Johnson BD, Dato ME, Kim YB

Author

Bryon D. Johnson PhD Adjunct Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Antibodies, Monoclonal
Antibody-Dependent Cell Cytotoxicity
Female
Granulocytes
Humans
In Vitro Techniques
Killer Cells, Natural
Male
Receptors, Fc
Swine
Swine, Miniature
Tumor Cells, Cultured