Document Detail

Intimate cell conjugate formation and exchange of membrane lipids precede apoptosis induction in target cells during antibody-dependent, granulocyte-mediated cytotoxicity.
MedLine Citation:
PMID:  17579054     Owner:  NLM     Status:  MEDLINE    
Ab-dependent polymorphonuclear granulocyte (PMN)-mediated cytotoxicity may play an important role in the control of malignant diseases. However, little is known as to which particular pathways are used for the killing of malignant cells by PMN. The production of reactive oxygen intermediates (ROI) has been observed to occur during Ab-dependent, cell-mediated cytotoxicity (ADCC). However, PMN from a patient with chronic granulomatous disease demonstrated strong ADCC against malignant lymphoma cells. Furthermore, the inhibition of ROI production in PMN from healthy donors had no significant effect on ADCC. Therefore, ROI production by the NADPH oxidase of PMN does not appear to be mandatory for PMN-mediated ADCC. Recent data suggest a role for perforins in PMN-mediated cytotoxicity. However, in our assays concanamycin A, an inhibitor of perforin-mediated ADCC by mononuclear cells, had no inhibitory effect on PMN-mediated ADCC. Using electron microscopy we observed that PMN and their target cells intimately interact with the formation of interdigitating membrane protrusions. During PMN and target cell contact there was a mutual exchange of fluorescent membrane lipid dyes that was strongly increased in the presence of tumor-targeting Abs. This observation may be closely related to the recently described process of trogocytosis by lymphocytes. The presence of transient PMN-tumor cell aggregates and the accumulation of PMN with tumor cell-derived membrane lipids and vice versa were associated with effective ADCC as measured by chromium-release or apoptosis induction.
Heike Horner; Carola Frank; Claudia Dechant; Roland Repp; Martin Glennie; Martin Herrmann; Bernhard Stockmeyer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  179     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-06-20     Completed Date:  2007-08-07     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  337-45     Citation Subset:  AIM; IM    
Institute for Clinical Immunology, Division of Hematology/Oncology, University of Erlangen-Nuremberg, Erlangen, Germany.
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MeSH Terms
Antibodies, Monoclonal / pharmacology
Antibody-Dependent Cell Cytotoxicity / drug effects,  immunology*
Antigens, CD19 / immunology
Apoptosis / drug effects,  immunology*
Cell Aggregation / immunology
Cell Line, Transformed
Cell Line, Tumor
HLA-D Antigens / immunology
Macrolides / pharmacology
Membrane Glycoproteins / antagonists & inhibitors
Membrane Lipids / metabolism*
Neutrophils / drug effects,  immunology*,  metabolism*,  ultrastructure
Pore Forming Cytotoxic Proteins / antagonists & inhibitors
Reactive Oxygen Species / metabolism
Receptor, erbB-2 / immunology
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antigens, CD19; 0/HLA-D Antigens; 0/Macrolides; 0/Membrane Glycoproteins; 0/Membrane Lipids; 0/Pore Forming Cytotoxic Proteins; 0/Reactive Oxygen Species; 126465-35-8/Perforin; 80890-47-7/concanamycin A; EC protein, human; EC, erbB-2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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