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Autocrine/paracrine modulation of polymorphonuclear leukocyte survival after exposure to Candida albicans
J F Sweeney1, P K Nguyen, G M Omann
1Department of Surgery, University of Michigan, Ann Arbor Veterans Affairs Medical Center, 48105, USA.
Abstract:
Polymorphonuclear leukocytes (PMN) play a central role in the host response to injury and infection. These terminally differentiated phagocytes have a limited life span, after which they undergo spontaneous apoptosis. PMN life span can be significantly prolonged by several naturally occurring cytokines, and PMN are now known to be capable of cytokine production in response to various antigenic stimuli. These facts suggest the possibility that PMN possess an autocrine/paracrine mechanism for the control of their own survival. The present study was undertaken to test this hypothesis. Supernatants from PMN that had been incubated with Candida albicans for 18 h significantly decreased the number of fresh PMN demonstrating features of apoptosis and increased the percentage of viable PMN during in vitro culture. This was demonstrated by monitoring morphologic features of apoptosis with fluorescence microscopy and DNA endonuclease activity with agarose gel electrophoresis. Significant levels of tumor necrosis factor (TNF) were detectable in the supernatants of PMN that had been stimulated with C. albicans, as determined using a TNF-sensitive cell line. Neutralization of TNF biologic activity with a specific monoclonal antibody partially abrogated the supernatant-mediated prolongation of PMN survival. The present study demonstrates that PMN possess a mechanism for the modulation of their own survival, which in part may be through the production of TNF.
Insights
Polymorphonuclear leukocytes (PMN) can prolong their own survival. Stimulation with Candida albicans leads to PMN producing tumor necrosis factor (TNF), which reduces PMN apoptosis and enhances survival.
Area of Science:
- Immunology
- Cell Biology
Background:
- Polymorphonuclear leukocytes (PMN) are crucial for host defense but have a short lifespan.
- PMN undergo spontaneous apoptosis, a process that can be modulated by cytokines.
Purpose of the Study:
- To investigate if PMN possess an autocrine/paracrine mechanism for survival control.
- To determine the role of PMN-derived cytokines in regulating their own lifespan.
Main Methods:
- Incubation of PMN with Candida albicans.
- Analysis of PMN apoptosis using fluorescence microscopy and DNA endonuclease activity.
- Detection of tumor necrosis factor (TNF) in PMN supernatants.
- Neutralization of TNF activity with monoclonal antibodies.
Main Results:
- Supernatants from C. albicans-stimulated PMN reduced apoptosis and increased viability of fresh PMN.
- Significant levels of TNF were detected in PMN supernatants.
- TNF neutralization partially blocked the survival-promoting effect of PMN supernatants.
Conclusions:
- PMN can modulate their own survival through an autocrine/paracrine mechanism.
- Tumor necrosis factor (TNF) production by PMN contributes to their prolonged survival.