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Role of macrophages in pulmonary late-phase reaction in guinea pigs
N Yamada1, H Inoue, T Takishima
1First Department of Internal Medicine Tohoku University School of Medicine, Senddi, Japan.
Abstract:
To examine the role of macrophages in pulmonary late-phase reaction (LPR), macrophages were reduced in sensitized guinea pigs by an intravenous injection of liposome-encapsulated dichloromethylene diphosphonate (Cl2MDP). Macrophage reduction was evaluated by bronchoalveolar lavage (BAL) fluid analysis. In Cl2MDP liposome-treated animals, the number of macrophages in BAL fluid significantly decreased by 56% compared with PBS liposome-treated animals (1.6 +/- 0.1 vs. 3.6 +/- 0.4 x 10(6) cells, p < 0.01). The number of neutrophils, eosinophils, or lymphocytes in BAL fluid showed no significant changes in these two groups. Both PBS and Cl2MDP liposome-treated sensitized guinea pigs were challenged with an inhalation of antigen, and respiratory resistance (Rrs) was measured. PBS liposome-treated animals (control) exhibited both immediate (IPR) and late (LPR) increases in Rrs. The maximal increases in Rrs at IPR and LPR were 217 +/- 19 and 187 +/- 20% of baseline values, respectively (n = 9). On the other hand, Cl2MDP liposome-treated animals showed an immediate increase in Rrs (IPR); however, the late increase in Rrs (LPR) was significantly suppressed (p < 0.05). The maximal increases in Rrs at IPR and LPR were 200 +/- 13 and 134 +/- 11% of baseline values, respectively (n = 8). In Cl2MDP liposome-treated animals, the numbers of macrophages and neutrophils in BAL fluid 4 hr after antigen challenge decreased by 45% and 54%, respectively, compared with PBS liposome-treated animals (p < 0.05). In Cl2MDP liposome-treated animals, neutrophil chemotactic activity in BAL fluid 4 hr after antigen challenge decreased by 59% compared with PBS liposome-treated animals (p < 0.05). These results suggest that macrophages play an important role in the development of pulmonary LPR through the induction of neutrophil accumulation in the airways.
Insights
Macrophages are crucial for the late-phase reaction (LPR) in the lungs. Reducing macrophages significantly suppressed LPR and neutrophil accumulation, indicating their key role in allergic airway inflammation.
Area of Science:
- Immunology
- Pulmonary Medicine
- Allergy Research
Background:
- Pulmonary late-phase reaction (LPR) is a key component of allergic airway inflammation.
- The precise role of macrophages in LPR development remains incompletely understood.
- Macrophages are immune cells involved in inflammatory responses.
Purpose of the Study:
- To investigate the role of macrophages in the development of pulmonary late-phase reaction (LPR).
- To determine if reducing macrophage numbers impacts LPR and associated inflammatory markers.
Main Methods:
- Sensitized guinea pigs were treated with liposome-encapsulated dichloromethylene diphosphonate (Cl2MDP) to deplete macrophages.
- Macrophage reduction was confirmed via bronchoalveolar lavage (BAL) fluid analysis.
- Respiratory resistance (Rrs) was measured after antigen challenge to assess immediate (IPR) and late (LPR) phase responses.
Main Results:
- Cl2MDP treatment significantly reduced macrophages in BAL fluid by 56% without affecting other immune cells.
- While immediate bronchoconstriction (IPR) was unaffected, Cl2MDP treatment significantly suppressed the late-phase reaction (LPR).
- Macrophage and neutrophil numbers, along with neutrophil chemotactic activity, were reduced in BAL fluid of Cl2MDP-treated animals post-challenge.
Conclusions:
- Macrophages play a significant role in the pathogenesis of pulmonary late-phase reactions.
- Macrophage depletion suppresses LPR, likely by reducing neutrophil recruitment to the airways.
- Targeting macrophages may offer a therapeutic strategy for allergic airway diseases.