Redistributions of macrophages expressing the macrophage galactose-type C-type lectin (MGL) during antigen-induced chronic granulation tissue formation

Abstract

Cell surface lectins are known to regulate trafficking of cells in the immune system, yet the role of macrophage galactose-type C-type lectin 1 and 2 (MGL1/2) is poorly understood. In this study, antigen-specific chronic inflammation was induced in a subcutaneous air pouch model in mice, and distribution of cells expressing MGL1/2 was investigated. Azobenzenearsonate-conjugated acetylated BSA, used as an antigen, was introduced into an air pouch of immunized mice, and tissue formation and distribution of MGL1/2-positive cells in the sub-dermal regions was examined. Thickness of the inflammatory tissue and number of MGL1/2-positive cells simultaneously reached the maximum at day 4 and returned to the control level at day 6 or 8. When additional antigenic challenges were given, a chronic granulation tissue, which had two distinct layers, was generated. In the chronic tissue, CD11b-positive/MGL1/2-negative cells were abundant in the area close to the antigenic stimulus, while the area far from the antigenic stimulus was dominated by MGL1/2-positive/CD11b-negative or -low cells. Flow cytometric analyses of isolated cells from the granulation tissue revealed that MGL1/2-positive cells expressed MHC class II at high levels, CD11b at low levels but no CD11c. MGL1/2-positive and -negative fractions were separated from cells in the granulation tissue and a higher level of IL-1alpha messenger RNA than negative populations was detected in the MGL1/2-positive fraction by the semi-quantitative reverse transcription-PCR method. IL-1alpha production by MGL1/2-positive cells was also immunohistochemically detected. Results suggest that MGL1/2-positive cells represent a distinct sub-population of macrophages, having unique functions in the generation and maintenance of granulation tissue induced by antigenic stimuli.