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Impairment of function in aging neutrophils is associated with apoptosis.

M K Whyte, L C Meagher, J MacDermot and C Haslett
J Immunol June 1, 1993, 150 (11) 5124-5134;
M K Whyte
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L C Meagher
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J MacDermot
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C Haslett
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Abstract

Neutrophil apoptosis or programmed cell death permits neutrophil recognition and ingestion by macrophages and represents a mechanism capable of promoting resolution of inflammation. The consequences of apoptosis for neutrophil function are the subject of these investigations. A direct relationship between apoptosis and loss of cytoskeletal functions, phagocytosis, degranulation, and respiratory burst was demonstrated by counterflow centrifugation of neutrophils (aged for 24 h in culture) into fractions with varying proportions of apoptosis. Apoptotic neutrophils displayed a loss of background functions: ability to spread and change shape and random migration. They also showed a reduced ability to respond to deliberate stimulation with the receptor-dependent stimulus, FMLP, by undergoing shape change, chemotaxis, degranulation, and respiratory burst, and showed an inability to phagocytose opsonized zymosan. Loss of FMLP binding to apoptotic neutrophils was demonstrated by analysis of FML[3H]P binding and by autoradiography. Superoxide anion production, but not shape change or degranulation response, to the receptor-independent stimulus, PMA, was preserved in apoptotic neutrophils, implying some retention of intracellular signaling pathways relevant to superoxide production. Apoptosis thus marks a loss of neutrophil functional responsiveness and defines the cell as effectively "isolated" from its external milieu. Neutrophil apoptosis may represent an important event in the control of inflammation, marking the neutrophil both for disposal and as a cell with profound loss of its capacity to generate and release histotoxic products on external stimulation.

  • Copyright © 1993 by American Association of Immunologists

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The Journal of Immunology
Vol. 150, Issue 11
1 Jun 1993
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Impairment of function in aging neutrophils is associated with apoptosis.
M K Whyte, L C Meagher, J MacDermot, C Haslett
The Journal of Immunology June 1, 1993, 150 (11) 5124-5134;

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Impairment of function in aging neutrophils is associated with apoptosis.
M K Whyte, L C Meagher, J MacDermot, C Haslett
The Journal of Immunology June 1, 1993, 150 (11) 5124-5134;
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Print ISSN 0022-1767        Online ISSN 1550-6606