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Intimate cell conjugate formation and exchange of membrane lipids precede apoptosis induction in target cells during antibody-dependent, granulocyte-mediated cytotoxicity

Intimate cell conjugate formation and exchange of membrane lipids precede apoptosis induction in target cells during antibody-dependent, granulocyte-mediated cytotoxicity
Intimate cell conjugate formation and exchange of membrane lipids precede apoptosis induction in target cells during antibody-dependent, granulocyte-mediated cytotoxicity
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.

0022-1767
337-345
Horner, Heike
41e8c0f5-496e-4abf-b530-6972a6e678ec
Frank, Carola
476c3dc3-5943-403f-8c8a-ad70f66b09a2
Dechant, Claudia
13dd6c6c-59ae-49f0-b538-4ef640cbf903
Repp, Roland
762b8881-3417-4c23-89c8-c2c44032b2bb
Glennie, Martin
9f6f0eff-4560-48c2-80cd-0ec116110ded
Herrmann, Martin
19b969fe-1771-4c6e-937c-9bc6c1a1c16a
Stockmeyer, Bernhard
dac08105-8b0d-4bb2-b486-1ae1f6df9557
Horner, Heike
41e8c0f5-496e-4abf-b530-6972a6e678ec
Frank, Carola
476c3dc3-5943-403f-8c8a-ad70f66b09a2
Dechant, Claudia
13dd6c6c-59ae-49f0-b538-4ef640cbf903
Repp, Roland
762b8881-3417-4c23-89c8-c2c44032b2bb
Glennie, Martin
9f6f0eff-4560-48c2-80cd-0ec116110ded
Herrmann, Martin
19b969fe-1771-4c6e-937c-9bc6c1a1c16a
Stockmeyer, Bernhard
dac08105-8b0d-4bb2-b486-1ae1f6df9557

Horner, Heike, Frank, Carola, Dechant, Claudia, Repp, Roland, Glennie, Martin, Herrmann, Martin and Stockmeyer, Bernhard (2007) Intimate cell conjugate formation and exchange of membrane lipids precede apoptosis induction in target cells during antibody-dependent, granulocyte-mediated cytotoxicity. Journal of Immunology, 179 (1), 337-345. (PMID:17579054)

Record type: Article

Abstract

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.

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Published date: 1 July 2007

Identifiers

Local EPrints ID: 169257
URI: http://eprints.soton.ac.uk/id/eprint/169257
ISSN: 0022-1767
PURE UUID: a0bc108c-7fa3-4ca3-a442-8b15a27b94da

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Date deposited: 13 Dec 2010 13:41
Last modified: 22 Jul 2022 17:33

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Contributors

Author: Heike Horner
Author: Carola Frank
Author: Claudia Dechant
Author: Roland Repp
Author: Martin Glennie
Author: Martin Herrmann
Author: Bernhard Stockmeyer

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