Role of macrophages in pulmonary late-phase reaction in guinea pigs.

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.