Alveolar macrophage-induced suppression of peripheral blood mononuclear cell responsiveness is reversed by in vitro allergen exposure in bronchial asthma

Little information is available on the specific role of alveolar macrophages (AMs) in modulating local cellular reactions to inhaled allergens in atopic asthma. We investigated the influence of alveolar macrophages obtained by bronchoalveolar lavage (BAL) on the proliferative responses of lavage and peripheral lymphocytes from 12 patients with atopic asthma, 6 nonasthmatic symptomatic atopic subjects, and 6 nonatopic normal volunteers, in the context of in vitro exposure to relevant and nonrelevant allergens. Fresh nonadherent bronchoalveolar lavage cells from atopic asthmatic patients, depleted of alveolar macrophages, proliferated spontaneously more than nonadherent bronchoalveolar lavage cells from normal subjects. Addition of autologous asthmatic alveolar macrophages reduced this endogenous "activation". Asthmatic and normal alveolar macrophages also inhibited phytohaemagglutinin-stimulated proliferation of both autologous and allogeneic nonadherent peripheral blood mononuclear cells (PBMC). In contrast, autologous asthmatic alveolar macrophages induced strong proliferation of peripheral blood mononuclear cells when stimulated with allergen to which the patient was skin test and radio allergosorbent test (RAST) reactive; however, no response was seen with allergens to which the patient was insensitive. No such allergen-specific proliferation was seen with alveolar macrophages from nonasthmatic atopic subjects. These data support the presence of functionally-active alveolar macrophages within the airways of atopic asthmatic patients, that under normal stable conditions suppress the induction of peripheral blood mononuclear cell responses, and which only on contact with specific allergen appear to switch to inducer alveolar macrophages, with consequent peripheral blood mononuclear cell hyperactivation.