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Originally published In Press as doi:10.1074/jbc.M512889200 on June 28, 2006
J. Biol. Chem., Vol. 281, Issue 37, 26792-26801, September 15, 2006
Serglycin Is the Major Secreted Proteoglycan in Macrophages and Has a Role in the Regulation of Macrophage Tumor Necrosis Factor- Secretion in Response to Lipopolysaccharide*
Lillian Zernichow 1,
Magnus Åbrink ,
Jenny Hallgren 2,
Mirjana Grujic 3,
Gunnar Pejler , and
Svein O. Kolset 4
From the
Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Box 1046 Blindern, 0316 Oslo, Norway and the Department of Molecular Biosciences, Biomedical Centre, Swedish University of Agricultural Sciences, Box 575, 75123 Uppsala, Sweden
It has recently been shown that serglycin is essential for maturation of mast cell secretory granules. However, serglycin is expressed also by other cell types, and in this study we addressed the role of serglycin in macrophages. Adherent cells were prepared from murine peritoneal cell populations and from spleens, and analyzed for proteoglycan synthesis by biosynthetic labeling with [35S]sulfate. Conditioned media from serglycin/ peritoneal macrophages and adherent spleen cells displayed a 6580% reduction of 35S-labeled proteoglycans, compared with corresponding material from serglycin+/+ cells, indicating that serglycin is the dominant secretory proteoglycan in macrophages of these origins. In contrast, the levels of intracellular proteoglycans were similar in serglycin+/+ and serglycin/ cells, suggesting that serglycin is not stored intracellularly to a major extent in macrophages. This is in contrast to mast cells, in which serglycin is predominantly stored intracellularly. Transmission electron microscopy revealed that the absence of serglycin did not cause any major morphological effects on peritoneal macrophages, in contrast to dramatic defects in intracellular storage vesicles in peritoneal mast cells. Several secretory products were not found to be affected by the lack of serglycin. However, the secretion of tumor necrosis factor- in response to lipopolysaccharide stimulation was markedly higher in serglycin/ cultures than in those of serglycin+/+. The present report thus demonstrates that serglycin is the major proteoglycan secreted by peritoneal macrophages and suggests that the macrophage serglycin may have a role in regulating secretion of tumor necrosis factor- .
Received for publication, December 2, 2005
, and in revised form, June 14, 2006.
* This work was supported in part by Grants from the Norwegian Cancer Society (Grant A88367
[GenBank]
), the AgriFunGen program at the Swedish University of Agricultural Sciences and the Swedish Research Council, King Gustaf V's 80th Anniversary Fund. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 Fellow of Norwegian Cancer Society.
2 Present address: Harvard Medical School, Div. of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115.
3 Present address: Inst. of Medical Microbiology and Immunology, University of Copenhagen, The Panum Institute, Blegdamsvej 3C, DK-2200 Copenhagen N, Denmark.
4 To whom correspondence should be addressed: Dept. of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Box 1046 Blindern, 0316 Oslo, Norway. Tel.: 47-22851383; Fax: 47-22851398; E-mail: s.o.kolset{at}medisin.uio.no.

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Copyright © 2006 by the American Society for Biochemistry and Molecular Biology.
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