Alternatively activated macrophage (AAM) phenotype induced in murine lungs by cockroach allergen (CRA) exposure (175.19)

• Published in: The Journal of immunology (1950) 2012-05, Vol.188 (1_Supplement), p.175-175.19
• Main Authors: Beal, Dominic, Stepien, David, Bouchard, Jacqueline, Kim, Jiyoun, Remick, Daniel
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.188.Supp.175.19

Human studies of asthma have shown that a subset of AAM is required for disease progression. These cells differ from classically activated macrophages (mϕ) in that they produce/induce production of Th2 cytokines and are comparably inefficient in antigen presentation. In this study a murine model of CRA-induced asthma was used to study mϕ phenotypes. To induce disease, mice were immunized intra-tracheally with CRA and challenged twice 14 and 21 days later. Mice were sacrificed after the 3rd challenge and compared to naïve controls. Enzymatic digests of whole lungs were analyzed by flow cytometry, and cultured to assess cytokine production. 24 hours after the final challenge, mϕ co-stimulatory molecule expression (CD80, CD86) was reduced, as compared to both pre-challenge and age-matched naïve control mice (~40% vs 60% CD86+ cells). This effect was limited to mϕ, as CD28 and CTLA4 on T lymphocytes were unaffected. ELISA performed on supernatants of cells cultured with CRA showed enhanced levels of IL4, 5, 10, and 13 (~60, 500, 350, and 1000pg/ml respectively, vs undetectable in controls) and reduced MIP1a(~2 vs 12 ng/ml), MIP2 (~10 vs 24ng/ml), and KC (~5 vs 9ng/ml). Mϕ isolated from the spleen and peritoneal cavity showed no significant differences in surface molecule expression, indicating these effects of CRA are limited to the lungs. These data show that CRA exposure results in the generation of an AAM-like phenotype in the lung. All p values for quoted data