Abstract
Cystatin C (gamma-trace) was found to be a constitutively secreted protein of isolated human monocytes and mouse peritoneal macrophages, as well as the histiocytic lymphoma cell lines U937, P388D.1, and J774. This proteinase inhibitor is not uniquely secreted by monocytes/macrophages, but was also identified in the conditioned media from several primary cells, including brain cells, and diverse established cell lines. In vitro treatment of resident mouse peritoneal macrophages with either LPS or IFN-gamma caused a downregulation in cystatin C secretion. Elaboration of this protein was also diminished by macrophages that had been stimulated by thioglycollate in vivo, and treatment of these cells with LPS led to further decline. It is suggested that, under some inflammatory conditions, downregulation of cystatin C may contribute to tissue pathology.
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Selected References
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- Barrett A. J., Davies M. E., Grubb A. The place of human gamma-trace (cystatin C) amongst the cysteine proteinase inhibitors. Biochem Biophys Res Commun. 1984 Apr 30;120(2):631–636. doi: 10.1016/0006-291x(84)91302-0. [DOI] [PubMed] [Google Scholar]
- Brzin J., Popovic T., Turk V., Borchart U., Machleidt W. Human cystatin, a new protein inhibitor of cysteine proteinases. Biochem Biophys Res Commun. 1984 Jan 13;118(1):103–109. doi: 10.1016/0006-291x(84)91073-8. [DOI] [PubMed] [Google Scholar]
- Cohen A. B. Interrelationships between the human alveolar macrophage and alpha-1-antitrypsin. J Clin Invest. 1973 Nov;52(11):2793–2799. doi: 10.1172/JCI107475. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ghiso J., Jensson O., Frangione B. Amyloid fibrils in hereditary cerebral hemorrhage with amyloidosis of Icelandic type is a variant of gamma-trace basic protein (cystatin C). Proc Natl Acad Sci U S A. 1986 May;83(9):2974–2978. doi: 10.1073/pnas.83.9.2974. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hovi T., Mosher D., Vaheri A. Cultured human monocytes synthesize and secrete alpha2-macroglobulin. J Exp Med. 1977 Jun 1;145(6):1580–1589. doi: 10.1084/jem.145.6.1580. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hubbard W. J. Alpha-2 macroglobulin-enzyme complexes as suppressors of cellular activity. Cell Immunol. 1978 Sep;39(2):388–394. doi: 10.1016/0008-8749(78)90114-4. [DOI] [PubMed] [Google Scholar]
- Löfberg H., Grubb A., Davidsson L., Kjellander B., Strömblad L. G., Tibblin S., Olsson S. O. Occurrence of gamma-trace in the calcitonin-producing C-cells of simian thyroid gland and human medullary thyroid carcinoma. Acta Endocrinol (Copenh) 1983 Sep;104(1):69–76. doi: 10.1530/acta.0.1040069. [DOI] [PubMed] [Google Scholar]
- Morse J. O. Alpha1-antitrypsin deficiency (second of two parts). N Engl J Med. 1978 Nov 16;299(20):1099–1105. doi: 10.1056/NEJM197811162992003. [DOI] [PubMed] [Google Scholar]
- Mosher D. F., Wing D. A. Synthesis and secretion of alpha2-macroglobulin by cultured human fibroblasts. J Exp Med. 1976 Feb 1;143(2):462–467. doi: 10.1084/jem.143.2.462. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Müller-Esterl W., Fritz H., Machleidt W., Ritonja A., Brzin J., Kotnik M., Turk V., Kellermann J., Lottspeich F. Human plasma kininogens are identical with alpha-cysteine proteinase inhibitors. Evidence from immunological, enzymological and sequence data. FEBS Lett. 1985 Mar 25;182(2):310–314. doi: 10.1016/0014-5793(85)80322-7. [DOI] [PubMed] [Google Scholar]
- Shtacher G., Maayan R., Feinstein G. Proteinase inhibitors in human synovial fluid. Biochim Biophys Acta. 1973 Mar 23;303(1):138–147. doi: 10.1016/0005-2795(73)90155-4. [DOI] [PubMed] [Google Scholar]
- Unkeless J. C., Gordon S., Reich E. Secretion of plasminogen activator by stimulated macrophages. J Exp Med. 1974 Apr 1;139(4):834–850. doi: 10.1084/jem.139.4.834. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Warfel A. H., Zucker-Franklin D. Down-regulation of macrophage lysozyme by lipopolysaccharide and interferon. J Immunol. 1986 Jul 15;137(2):651–655. [PubMed] [Google Scholar]
- Zucker-Franklin D., Warfel A., Grusky G., Frangione B., Teitel D. Novel monocyte-like properties of microglial/astroglial cells. Constitutive secretion of lysozyme and cystatin-C. Lab Invest. 1987 Aug;57(2):176–185. [PubMed] [Google Scholar]