ROLE OF MACROPHAGES IN PULMONARY LATE-PHASE REACTION IN GUINEA-PIGS

To examine the role of macrophages in pulmonary late-phase reaction (L PR), macrophages were reduced in sensitized guinea pigs by an intraven ous injection of liposome-encapsulated dichloromethylene diphosphonate (Cl(2)MDP). Macrophage reduction was evaluated by bronchoalveolar lav age (BAL) fluid analysis. In Cl(2)MDP liposome-treated animals, the nu mber of macrophages in BAL fluid significantly decreased by 56% compar ed with PBS liposome-treated animals (1.6+/-0.1 vs. 3.6+/-0.4x10(6) ce lls, p <0.01). The number of neutrophils, eosinophils, or lymphocytes in BAL fluid showed no significant changes in these two groups. Both P BS and Cl(2)MDP liposome-treated sensitized guinea pigs were challenge d with an inhalation of antigen, and respiratory resistance (Rrs) was measured. PBS liposome-treated animals (control) exhibited both immedi ate (IPR) and late (LPR) increases in Rrs. The maximal increases in Rr s at IPR and LPR were 217+/-19 and 187+/-20% of baseline values, respe ctively (n=9). On the other hand, Cl(2)MDP liposome-treated animals sh owed an immediate increase in Rrs (IPR); however, the late increase in Rrs (LPR) was significantly suppressed (p <0.05). The maximal increas es in Rrs at IPR and LPR were 200+/-13 and 134+/-11% of baseline value s, respectively (n=8). In Cl(2)MDP liposome-treated animals, the numbe rs of macrophages and neutrophils in BAL fluid 4 hr after antigen chal lenge decreased by 45% and 54%, respectively, compared with PBS liposo me-treated animals (p <0.05). In Cl(2)MDP liposome-treated animals, ne utrophil chemotactic activity in BAL fluid 4 hr after antigen challeng e decreased by 59% compared with PBS liposome-treated animals (p <0.05 ). These results suggest that macrophages play an important role in th e development of pulmonary LPR through the induction of neutrophil acc umulation in the airways.