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Alternative activation of macrophages during the allergic airway inflammation alters antigen presenting capacities

: Winkler, Carla; Carstens, Hauke; Müller, Meike; Schaumann, Frank; Faulenbach, Cornelia; Hohlfeld, Jens M.

American Journal of Respiratory and Critical Care Medicine 185 (2012), Abstract A5053
ISSN: 1073-449X
ISSN: 0003-0805
ISSN: 1535-4970
American Thoracic Society (ATS International Conference) <2012, San Francisco/Calif.>
Fraunhofer ITEM ()

Alveolar Macrophages (AM) play an important role in the innate and adaptive immune response of the lung. During pulmonary infection and allergic airway inflammation AM can be activated and polarized. The alternatively activated phenotype (aaM) is induced by interleukin (IL)-4, a cytokine which is increased during the allergic inflammation. However, the functional role of aaM during the allergic airway response is poorly understood. Therefore, we characterized aaM with regard to the adaptive immune response.
Macrophages and dendritic cells (DCs) were generated from human peripheral blood monocytes of atopic donors and aaM were induced in the presence of IL-4. DCs, M and aaM were stimulated with allergen and co-cultured with autologous CD4+ T-lymphocytes. Additionally human AM were isolated from bronchoalveolar lavage (BAL) following segmental allergen provocation and co-cultured with autologous CD4+ T-lymphocytes in the presence or absence of allergen. T-lymphocyte proliferation was assessed by 3H-thymidine incorporation and alternative activation of human macrophages was further characterized by flow cytometric analysis of co-stimulatory surface markers (HLA-DR, CD86 and CD206).
Unlike DCs, allergen-stimulated M induced no proliferation of antigen-specific CD4+ T-lymphocytes. However, aaM exhibited enhanced antigen presenting capacities, inducing a significant increase of T-lymphocyte proliferation (n=7, p<0.01). In accordance, AM isolated from BAL fluid after segmental allergen challenge, induced proliferation of CD4+ T-lymphocytes which was further increased after re-stimulation with the appropriate allergen (n=4, p<0.05). In contrast, AM isolated from the saline (control) segment induced only proliferation after re-stimulation with allergen. However, the proliferation index was rather low compared to macrophages from the allergen segment. Further,
expression of co-stimulatory surface molecules HLA-DR, CD86 (p<0.05) and CD206 (p<0.1) were up-regulated on AM after segmental allergen challenge compared to control.
Both in vitro generated aaM and primary AM isolated after segmental allergen challenge displayed an alternatively activated phenotype resulting in functional alterations with increased T-lymphocyte proliferation. Endocytosis as well as the expression of co-stimulatory molecules was increased in alternatively activated macrophages which enabled antigen presentation and thus induction of specific T-lymphocyte proliferation. Our data reveal that alternatively activated macrophages contribute to the adaptive immune response underlying the allergic airway inflammation.