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Interleukin-2 prevention of apoptosis in human neutrophils
1H. Lee Moffitt Cancer Center, University of South Florida College of Medicine, Tampa 33612.
Abstract:
Evidence is presented that interleukin (IL)-2 maintains viability of human polymorphonuclear cells (PMN) in culture by preventing these cells from undergoing programmed cell death (PCD) and induces the synthesis of new RNA and protein. Our laboratory has recently discovered that human PMN constitutively express IL-2 beta receptor and more importantly, PMN are able to respond functionally to IL-2 by enhanced growth inhibitory activity against an opportunistic fungal pathogen, Candida albicans. We now report that IL-2 was able to interfere with the PCD process and reduce the number of apoptotic PMN to < 40% in 72-h culture. Freshly isolated PMN usually underwent a time-dependent aging process and > 80% of PMN cultured in medium alone for 72 h showed morphologic features of PCD as depicted by hematoxylin and eosin staining as well as by electron microscopy. During the PCD process, untreated PMN not only exhibited condensed nuclear structure and decrease in cell size, but also displayed DNA fragmentation. DNA fragmentation in PMN was prevented by IL-2. Prevention of PCD by IL-2 was associated with an increase in new RNA and protein synthesis in PMN, which may reflect cytokine induction, such as tumor necrosis factor, as we have recently shown. Thus, our data expands our current understanding of PMN in that they may be an active component of the immune system, with a longer life-span when activated than expected.
Insights
Interleukin-2 (IL-2) prevents programmed cell death (PCD) in human polymorphonuclear cells (PMN), extending their lifespan. IL-2 also enhances PMN
Area of Science:
- Immunology
- Cell Biology
Background:
- Human polymorphonuclear cells (PMN) typically undergo programmed cell death (PCD) within 72 hours in culture.
- PMN constitutively express the IL-2 beta receptor and can respond to IL-2.
- IL-2 has shown potential in enhancing PMN's ability to inhibit Candida albicans growth.
Purpose of the Study:
- To investigate the effect of IL-2 on PMN viability and programmed cell death (PCD).
- To determine if IL-2 influences RNA and protein synthesis in PMN.
- To explore IL-2's role in preventing DNA fragmentation during PMN PCD.
Main Methods:
- Culturing human PMN with and without IL-2 for 72 hours.
- Assessing PMN viability and morphological features of PCD using hematoxylin and eosin staining and electron microscopy.
- Analyzing DNA fragmentation, RNA, and protein synthesis in PMN.
Main Results:
- IL-2 significantly reduced PMN PCD, with less than 40% showing apoptotic features after 72 hours, compared to over 80% in control cultures.
- IL-2 prevented DNA fragmentation in PMN during the PCD process.
- IL-2 treatment increased RNA and protein synthesis in PMN, potentially indicating cytokine induction.
Conclusions:
- IL-2 actively maintains human PMN viability by inhibiting PCD.
- IL-2's prevention of PCD is linked to increased RNA and protein synthesis in PMN.
- These findings suggest PMN may have a longer lifespan and play a more active immune role than previously understood.