title: Serglycin is the major secreted proteoglycan in macrophages and has a role in the regulation of macrophage tumor necrosis factor-alpha secretion in response to lipopolysaccharide.
abstract: 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 65-80% 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-alpha 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-alpha.
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Box 1046 Blindern, 0316 Oslo, Norway.
authors.forename: Lillian
authors.initials: L
authors.lastname: Zernichow
authors.forename: Magnus
authors.initials: M
authors.lastname: Abrink
authors.forename: Jenny
authors.initials: J
authors.lastname: Hallgren
authors.forename: Mirjana
authors.initials: M
authors.lastname: Grujic
authors.forename: Gunnar
authors.initials: G
authors.lastname: Pejler
authors.forename: Svein O
authors.initials: SO
authors.lastname: Kolset
mesh_terms: D000818:Animals; D005260:Female; D005786:Gene Expression Regulation; D008070:Lipopolysaccharides / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010537:Peritoneum / Q000473:pathology; D011509:Proteoglycans / Q000737:chemistry* / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D011509:Proteoglycans; D014409:Tumor Necrosis Factor-alpha; D033921:Vesicular Transport Proteins; C075430:serglycin