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Ultraviolet irradiation accelerates apoptosis in human polymorphonuclear leukocytes: protection by LPS and GM-CSF
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 host response to injury and infection. Understanding factors that regulate PMN survival may therefore have a major influence on the development of novel treatment strategies for controlling life-threatening infections, as well as local and systemic inflammatory responses. Unfortunately, the presently utilized in vitro culture model of PMN apoptosis makes the examination of early biochemical events surrounding PMN apoptosis very difficult. This study demonstrates that a short course of UV irradiation (15 min) can be used to induce rapid progression of PMN through the apoptotic process with 70-90% of PMN displaying features of apoptosis by 4 h after UV exposure. Bacterial lipopolysaccharide and granulocyte-macrophage colony-stimulating factor, which are known to prolong PMN survival during in vitro culture, also protected PMN from UV-accelerated apoptosis. The UV-accelerated model of PMN apoptosis provides another valuable tool for the investigation of early signaling pathways associated with inducing or delaying PMN apoptosis.
Insights
UV irradiation rapidly induces polymorphonuclear leukocyte (PMN) apoptosis in vitro. This accelerated model aids research into PMN survival factors and inflammatory responses, crucial for developing new infection treatments.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Polymorphonuclear leukocytes (PMN) are critical in host defense against infection and injury.
- Regulating PMN survival is key for developing treatments for infections and inflammatory conditions.
- Current in vitro models hinder the study of early biochemical events in PMN apoptosis.
Purpose of the Study:
- To develop an accelerated in vitro model for studying polymorphonuclear leukocyte (PMN) apoptosis.
- To investigate the effects of UV irradiation on PMN apoptosis progression.
- To assess the protective effects of known PMN survival factors in this new model.
Main Methods:
- Exposing PMNs to a short course of UV irradiation (15 min) to induce apoptosis.
- Quantifying PMN apoptosis features at 4 hours post-irradiation.
- Evaluating the impact of bacterial lipopolysaccharide (LPS) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on UV-accelerated apoptosis.
Main Results:
- UV irradiation (15 min) induced rapid PMN apoptosis, with 70-90% showing apoptotic features by 4 hours.
- Bacterial LPS and GM-CSF demonstrated a protective effect, delaying UV-induced PMN apoptosis.
- The UV-accelerated model effectively allowed examination of early apoptotic events.
Conclusions:
- UV irradiation provides a rapid and reliable method to induce PMN apoptosis in vitro.
- This model facilitates the study of signaling pathways involved in PMN apoptosis regulation.
- Findings support the development of novel therapeutic strategies targeting PMN survival in inflammatory diseases and infections.