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Comparative physiology of rodent pulmonary macrophages: in vitro functional responses
D B Warheit1, M A Hartsky, M S Stefaniak
1E.I. du Pont de Nemours and Co., Inc., Haskell Laboratory for Toxicology and Industrial Medicine, Newark, Delaware 19714.
Abstract:
Since toxicological testing of inhaled materials frequently requires utilization of several species, we have investigated pulmonary macrophage (PM) functional responses and compared the rat model with other rodents. Two strains of rats, three strains of mice, and one strain each of hamster and guinea pig were used in this study. The numbers of recovered cells by bronchoalveolar lavage generally correlated with animal body weight. The one exception was the Syrian Golden hamster from which increased numbers of macrophages were recovered. Cellular differential data obtained from lavaged cytocentrifuge preparations demonstrated that PM's account for greater than 97% of recoverable free lung cells for all species except the guinea pig, which contains a resident population of eosinophils. Cell morphology studies indicated that hamster PM exhibited the highest proportion of ruffled PM and demonstrated the highest phagocytic activity, whereas mouse PM phagocytic activity was significantly reduced compared with the other three species. In addition, chemotaxis studies showed that rat PM migrated best to zymosan-activated, complement-dependent chemoattractants, whereas hamster PM demonstrated an enhanced chemotactic response to N-formyl peptides. The results of these studies suggest that the rat may be the most efficient species for clearing inhaled particles, whereas hamsters and guinea pigs may best respond to bacteria.
Insights
Comparing rodent models for inhaled substance toxicology, this study found rats efficiently clear particles. Hamsters and guinea pigs show better responses to bacteria, highlighting species-specific pulmonary macrophage (PM) functions.
Area of Science:
- Comparative toxicology
- Pulmonary immunology
- In vivo rodent models
Background:
- Inhaled substance toxicological testing often requires multiple animal species.
- Understanding pulmonary macrophage (PM) function across species is crucial for accurate risk assessment.
- Rodent models are commonly used, but their comparative pulmonary responses are not fully characterized.
Purpose of the Study:
- To investigate and compare pulmonary macrophage (PM) functional responses in various rodent species.
- To evaluate the suitability of different rodent models for toxicological studies of inhaled materials.
- To determine species-specific differences in PM phagocytosis and chemotaxis.
Main Methods:
- Bronchoalveolar lavage (BAL) was performed on rats, mice, hamsters, and guinea pigs.
- Cellular differentials, morphology, phagocytic activity, and chemotaxis assays were conducted on recovered lung cells.
- Quantitative analysis of macrophage populations and their functional characteristics was performed.
Main Results:
- Macrophage recovery in BAL generally correlated with body weight, with Syrian Golden hamsters showing disproportionately high numbers.
- Hamster PM exhibited the highest phagocytic activity and a high proportion of ruffled cells.
- Rat PM showed optimal migration to complement-dependent chemoattractants, while hamster PM responded better to N-formyl peptides.
Conclusions:
- The rat model appears most efficient for studying particle clearance due to superior PM phagocytosis and migration.
- Hamsters and guinea pigs may be more suitable models for investigating bacterial responses due to distinct PM chemotaxis.
- Species-specific differences in pulmonary macrophage function necessitate careful selection of animal models in toxicological research.