Macrophages play important roles in immunity and
inflammation, and in allergic, granulomatous and neoplastic diseases. Here, we present the indepth results of an ongoing study of macrophage differentiation pathways in cutaneous macrophage disorders and in vitro. Up to now, a total of 40 cases of cutaneous macrophage disorders (
histiocytoses and
granulomas) and related diseases were examined using a panel of monoclonal and polyclonal
antibodies to macrophage
differentiation antigens (mAb MS-1, mAb alpha CD1a, mAb alpha CD34, mAb RM 3/1, mAb alpha CD11c, mAb alpha CD36, mAb MAC 387, mAb 27E10, polyclonal
antibodies alpha MRP-8 and -14, mAb alpha CD68, mAb 25F9, mAb DRC1-R4/23, and mAb 1F10). Of these, MS-1 high molecular weight
protein, synthesized by non-continuous sinusoidal endothelial cells and highly dendritic perivascular macrophages in normal human organs, is the most specific macrophage
differentiation marker. MS-1 high molecular weight
protein is selectively expressed by cutaneous non-Langerhans cell histocytoses, and proves to be a valuable diagnostic tool for these diseases. MS-1 high molecular weight
protein is not found in
Langerhans cell histiocytosis cells, epithelioid cells in
sarcoidosis, and palisading histiocytes in
granuloma annulare. MS-1+ macrophages may be found intermingled in cellular type
dermatofibroma and in
foreign body granulomas; they differ from MS-1+
non-Langerhans cell histiocytosis cells by their highly dendritic morphology, and thus rather resemble the MS-1+ macrophages in normal skin. RM 3/1
antigen shows a similar, but broader expression pattern including non-
Langerhans cell histiocytoses, xanthelasmata palpebrarum,
foreign body granulomas,
granuloma annulare, and cellular type
dermatofibroma. Moreover, xanthelasmata palpebrarum paradigmatically represent a class of macrophage lesions with strong RM 3/1, but little MS-1
antigen expression. In
sarcoidosis, RM 3/1+ macrophages are only found at the very periphery of epithelioid cell
granulomas. In contrast, 25F9
antigen is strongly and consistently expressed in epithelioid cells of
sarcoidosis, and in
foreign body granulomas. In cultured human monocytes/macrophages, RM 3/1
antigen is expressed early on, while MS-1 high molecular weight
protein and 25F9
antigen are late and very late macrophage
differentiation antigens, respectively. Expression of RM 3/1
antigen and MS-1 high molecular weight
protein is inducible by
glucocorticoid and
interleukin-4, and less so by
interleukin-13 and
interleukin-10, and combinations thereof, while 25F9
antigen seems to be less influenced by these agents.
Interferon-gamma (and less so
tumor necrosis factor-alpha) inhibit expression of all three
antigens in cultured human monocytes/macrophages.(ABSTRACT TRUNCATED AT 400 WORDS)