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Functional heterogeneity of colony-stimulating factor-induced human monocyte-derived macrophages AKAGAWA KS, KOMURO I, KANAZAWA H, YAMAZAKI T, MOCHIDA K, KISHI F. Respirology 2006; 11 : S32-S36 Objectives: Macrophages (M φ s) have various functions and play a critical role in host defense and the maintenance of homeostasis. M φ s exist in every tissue in the body, but M φ s from different tissues exhibit a wide range of phenotypes with regard to their morphology, cell surface antigen expression and function, and are called by different names. However, the precise mechanism of the generation of macrophage heterogeneity is not known. In the present study, the authors examined the functional heterogeneity of M φ s generated from human monocytes under the influence of granulocytemacrophage colony-stimulating factor (GM-CSF) and macrophage-CSF (M-CSF). Methodology: CD14 positive human monocytes (Mos) were incubated with M-CSF and GM-CSF for 6-7 days to stimulate the generation of M-CSF-induced monocyte-derived M φ s (M-M φ s) and GM-CSF-induced monocyte-derived M φ s (GM-M φ s), respectively. The expression of cell surface antigens and several functions such as antigen presenting cell activity, susceptibility to oxidant stress, and the susceptibility to HIV-1 and mycobacterium tuberculosis infection were examined. Results: GM-M φ s and M-M φ s are distinct in their morphology, cell surface antigen expression, and functions examined. The phenotype of GM-M φ s closely resembles that of human Alveolar-M φ s (A-M φ s), indicating that CSF-induced human monocyte-derived M φ s are useful to clarify the molecular mechanism of heterogeneity of human M φ s, and GM-M φ s will become a model of human A-M φ s.

We generated interleukin-5 receptor alpha chain (IL-5R alpha)-deficient (IL-5R alpha-/-) mice by gene targeting. The IL-5R alpha-/- mice showed decreased numbers of B-1 cells concomitant with low serum concentrations of IgM and IgG3. They showed no IL-5-induced enhancement of B cell responses to T-independent antigens. The number of alpha beta T cell receptor-positive thymocytes tended to decrease in 3-week-old IL-5R alpha-/- mice, returning to normal by 6 weeks of age. The IL-5R alpha-/- mice produced basal levels of eosinophils, while their bone marrow cells failed to form eosinophilic colonies in response to IL-5. Impaired eosinophilopoiesis in IL-5R alpha-/-mice enhanced the survival of Angiostrongylus cantonensis. These results indicate that IL-5-induced eosinophils serve as potent effector cells in the killing of Angiostrongylus cantonensis in mice.

Iba1 is a macrophage/microglia-specific calcium-binding protein that is involved in RacGTPase-dependent membrane ruffling and phagocytosis. In this study, we introduced Iba1 into Swiss 3T3 fibroblasts and demonstrated the enhancement of platelet-derived growth factor (

Anti-cytokine autoantibodies in healthy individuals have been widely reported but the occurrence is variable and inconstant. We hypothesized that cytokine-binding in vivo may explain their variable and infrequent detection. Therefore, we focused on the detection of the cytokine-autoantibody complexes and found that anti-cytokine autoantibody to IL-2, IL-8, tumor necrosis factor-a, vascular endothelial growth factor and granulocyte-colony stimulating factor were present in all 15 individuals evaluated, while those to IL-3, osteopontin and macrophage-colony stimulating factor were not detected in anyone. Autoantibodies against IL-4, IL-6, IL-10, and interferon-gamma were variously detected. Thus, we discovered that anti-cytokine autoantibodies to multiple cytokines are ubiquitous in healthy individuals.