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Modulation of rat granulocyte traffic by a surface active agent in vitro and bleomycin injury
1Division of Pulmonary and Critical Care Medicine, University of California Irvine Medical Center, Orange 92668.
Abstract:
Pluronic F68 (F68) is a nonionic surfactant which has been reported to inhibit the in vitro adherence and migration of polymorphonuclear leukocytes (PMN) obtained from some species. We demonstrated similar effects on PMN obtained from rats, with diminished adherence to nylon wool and diminished chemotaxis toward zymosan-activated serum. We then examined the in vivo effects of 12-hr F68 infusion on the injury induced by intratracheal bleomycin instillation (ITB) in rats. When sacrificed 24 hr following injury, rats demonstrated neutrophilia, neutrophil-prominent lung lavage cellularity, and increased lung weights. F68 decreased lavage leukocyte counts and lung weight gain in ITB-injured animals. Lung weights of ITB-injured animals correlated (r = 0.81, P less than 0.001) with logarithmic values of lavage PMN. F68 also enhanced neutrophilia and decreased spleen weight gain in injured animals. The acute effects of F68 on circulating leukocyte counts, osmolality, and total complement were also examined. The data demonstrate that F68 can affect PMN traffic both in vitro and in vivo. The data also confirm the prominence of PMN in lavage fluid early in ITB injury, and suggest that an influx of relatively few PMN is associated with lung weight gain in this model.
Insights
Pluronic F68 (F68) reduces inflammatory cell accumulation in the lungs following bleomycin injury in rats. This surfactant impacts polymorphonuclear leukocyte (PMN) behavior, decreasing lung inflammation and weight gain.
Area of Science:
- Biomedical Engineering
- Pulmonary Medicine
- Pharmacology
Background:
- Pluronic F68 (F68), a nonionic surfactant, is known to inhibit polymorphonuclear leukocyte (PMN) adherence and migration in vitro.
- The role of F68 in modulating inflammatory responses in vivo, particularly in lung injury models, requires further investigation.
Purpose of the Study:
- To investigate the in vivo effects of Pluronic F68 (F68) on lung injury induced by intratracheal bleomycin instillation (ITB) in rats.
- To assess the impact of F68 on PMN traffic and associated inflammatory markers in this acute lung injury model.
Main Methods:
- Rats received a 12-hour infusion of F68 prior to intratracheal bleomycin instillation.
- Lung lavage cellularity, lung weights, and spleen weights were measured 24 hours post-injury.
- Circulating leukocyte counts, osmolality, and total complement levels were also analyzed.
Main Results:
- F68 administration significantly decreased lavage leukocyte counts and lung weight gain in ITB-injured rats.
- A strong correlation was observed between lung weight gain and logarithmic values of lavage PMN.
- F68 also influenced circulating neutrophilia and reduced spleen weight gain in injured animals.
Conclusions:
- Pluronic F68 (F68) demonstrates efficacy in modulating PMN traffic both in vitro and in vivo.
- F68 treatment mitigates the inflammatory response in an acute rat lung injury model.
- The findings highlight the critical role of PMN influx in early ITB-induced lung injury and suggest F68 as a potential therapeutic agent.