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Adoptive Transfer of Alveolar Macrophages Abrogates Bronchial Hyperresponsiveness

Centre de Recherche, Hôpital Laval, Institut Universitaire de Cardiologie et de Pneumologie de l'Université Laval, Québec, Canada

Address correspondence to: Eric Careau, Centre de Recherche en Pneumologie, Hôpital Laval, 2725, Chemin Sainte-Foy, Sainte-Foy, QC, Canada G1V 4G5. E-mail: eric.careau{at}crhl.ulaval.ca

Increasing evidence suggests that alveolar macrophages (AM) are involved in asthma pathogenesis. To better understand the role that these cells play, we investigated the capacity of AM from allergy-resistant rat, Sprague Dawley (SD), to modulate airway hyperresponsiveness of allergy-susceptible rat, Brown Norway (BN). AM of ovalbumin (OVA)-sensitized BN rats were eliminated by intratracheal instillation of liposomes containing clodronate. AM from OVA-sensitized SD rats were transferred into AM-depleted BN rats 24 h before allergen challenge. Airway responsiveness to methacholine was measured the following day. Instillation of liposomes containing clodronate in BN rats eliminated 85% AM after 3 d compared with saline liposomes. Methacholine concentration needed to increase lung resistance by 200% (EC₂₀₀R_L) was significantly lower in OVA-challenged BN rats (27.9 ± 2.8 mg/ml) compared with SD rats (63.9 ± 8.6 mg/ml). However, when AM from SD rats were transferred into AM-depleted BN rats, airway responsiveness (64.0 ± 11.3 mg/ml) was reduced to the level of naïve rats (54.4 ± 3.7 mg/ml) in a dose-dependent manner. Interestingly, transfer of AM from BN rats into SD rats did not modulate airway responsiveness. To our knowledge, this is the first direct evidence showing that AM may protect against the development of airway hyperresponsiveness.

Abbreviations: alveolar macrophages, AM • bronchoalveolar lavage, BAL • Brown Norway, BN • dichloromethylene-diphosphate, Cl₂MDP • methacholine concentration needed to increase lung resistance by 200%, EC₂₀₀R_L • immunoglobulin, Ig • interleukin, IL • ovalbumin, OVA • pulmonary resistance, R_L • Sprague Dawley, SD • T helper, Th • tumor necrosis factor, TNF

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