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Acute lung inflammation in rats induced by phorbol myristate acetate (PMA)
J S Kerr1, A Ciuffetelli, H D Hall
1Medical Products Department, E. I. Du Pont de Nemours & Company, Wilmington, DE 19898.
Abstract:
Intratracheal administration of PMA produces acute lung injury in part due to the generation of O2-derived free radicals. This study evaluated the role of the antioxidant enzyme superoxide dismutase (SOD) in PMA-induced lung injury in the rat. PMA was instilled into rats intratracheally (20-60 micrograms/kg), and the lungs were lavaged 4 hr later. Total number of cells recovered from lavage after PMA treatment was not different from the total number recovered from controls; lavagable PMNs increased in a dose-dependent manner. Albumin in lavage fluid (an index of lung vascular permeability) was significantly increased at 60 micrograms/kg PMA. SOD (10,000 U) + PMA (60 micrograms/kg) reduced the albumin level but significantly increased both total number of cells and number of PMNs recovered from lavage fluid. To investigate the possibility that SOD decreases the ability of PMNs to adhere, PMN aggregation was measured in vitro. The results indicated that 10,000 U SOD can inhibit PMA-induced aggregation by 50%. In contrast, aggregation to other stimuli (e.g., fMet-Leu-Phe, A23187) was unaffected by SOD. We conclude SOD prevents PMA-induced lung permeability and diminishes PMN adherence.
Insights
Superoxide dismutase (SOD) prevents lung injury caused by phorbol myristate acetate (PMA) by reducing vascular permeability. SOD also inhibits polymorphonuclear neutrophil (PMN) adherence, a key factor in lung inflammation.
Area of Science:
- Pulmonary Medicine
- Biochemistry
- Inflammation Research
Background:
- Phorbol myristate acetate (PMA) induces acute lung injury via oxygen-derived free radicals.
- Polymorphonuclear neutrophils (PMNs) play a crucial role in the inflammatory response during lung injury.
Purpose of the Study:
- To investigate the protective role of superoxide dismutase (SOD), an antioxidant enzyme, against PMA-induced lung injury in rats.
- To determine the effect of SOD on PMN infiltration and adherence in the context of lung injury.
Main Methods:
- Intratracheal administration of varying doses of PMA to rats.
- Lung lavage performed 4 hours post-administration to quantify cellular content and albumin levels.
- In vitro measurement of PMN aggregation in response to PMA and other stimuli with and without SOD treatment.
Main Results:
- PMA treatment increased PMN count and albumin levels in lavage fluid in a dose-dependent manner.
- Co-administration of SOD with PMA reduced albumin levels, indicating decreased vascular permeability.
- SOD significantly inhibited PMA-induced PMN aggregation in vitro, but not aggregation induced by other stimuli.
Conclusions:
- Superoxide dismutase (SOD) effectively prevents PMA-induced acute lung injury by reducing vascular permeability.
- SOD diminishes PMN adherence and aggregation, suggesting a mechanism for its protective effect in lung inflammation.
- The findings highlight SOD's potential as a therapeutic agent for inflammatory lung conditions.