Altered antigen presentation properties of macrophages during the allergic airway inflammation

Introduction: Alveolar Macrophages (AMΦ) play an important role in the innate and adaptive immune response of the lung. During pulmonary infection and allergic airway inflammation AMΦ can be activated and polarized. The alternatively activated phenotype (aaMΦ) is induced by interleukin (IL)-4, a cytokine which is present during an allergic airway inflammation. However, the functional role of aaMΦ during an allergic airway inflammation is poorly understood. Thus, we characterized aaMΦ with regard to the adaptive immune response underlying the inflammation.

Methods: Murine bone marrow derived macrophages (BMDMs) were stimulated with ovalbumin in the presence or absence of IL-4 and co-cultured with ovalbumin specific T-lymphocytes.

Additionally, macrophages were generated from human blood monocytes of atopic donors and stimulated with allergen in the presence or absence of IL-4 and co-cultured afterwards with autologues T-lymphocytes. Primary macrophages were also isolated from human bronchoalveolar lavage (BAL) after segmental allergen provocation and co-cultured with T-lymphocytes in the presence or absence of allergen. T-lymphocyte proliferation was assessed by ³H-thymididne incorporation and alternative activation of human macrophages was characterized by analysis of co-stimulatory surface markers and expression of candidate marker genes by real-time PCR.

Results: IL-4 induced an alternatively activated phenotype in BMDMs. This was similar to isolated alveolar macrophages from mice in an acute asthma model with regards to the expression of marker genes. Interestingly antigen presenting capacities of murine aaBMDMs were markedly increased compared to naïve macrophages.

Additionally, human aaMΦ induced a prominent T-lymphocyte proliferation when compared to unstimulated macrophages. Co-stimulatory surface molecule expression (HLA-DR, CD86) was also increased on these cells, as well as endocytosis of a model allergen.

Discussion: We analyzed the functional role of aaMΦ in the context of allergic airway inflammation, where antigen presentation is essential for the initiation and progression of the acute inflammation. The prominent induction of T-lymphocyte proliferation after allergen stimulation of aaMΦ was comparable between the different in vitro models, using generated as well as primary isolated macrophages. Enhanced antigen presentation might be due to increased endocytosis of allergens by these cells and further up-regulation of co-stimulatory molecules. Our results indicate that the presence of aaMΦ during an allergic inflammation might contribute to the progression of the adaptive immune response.