Abstract
Heparan sulfate proteoglycan associated with endothelial cells in normal blood vessels inhibits intravascular coagulation and egress of blood cells and plasma proteins, key features of hyperacute rejection. It was shown herein that exposure of cultured porcine endothelium to human serum as a source of natural antibodies and complement caused cleavage and release of 5% of endothelial cell proteoglycans within 4 min and greater than 50% within 1 h. Proteoglycan release depended on activation of the classical complement pathway and preceded irreversible cell injury. These findings suggest that loss of endothelial cell proteoglycan may be a critical step in the pathogenesis of hyperacute rejection and in diseases involving humoral injury to endothelial cells.
Full Text
The Full Text of this article is available as a PDF (384.4 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Boyden S. V. Natural antibodies and the immune response. Adv Immunol. 1966;5:1–28. doi: 10.1016/s0065-2776(08)60271-0. [DOI] [PubMed] [Google Scholar]
- Calne R. Y. Organ transplantation between widely disparate species. Transplant Proc. 1970 Dec;2(4):550–556. [PubMed] [Google Scholar]
- Gallagher J. T., Lyon M., Steward W. P. Structure and function of heparan sulphate proteoglycans. Biochem J. 1986 Jun 1;236(2):313–325. doi: 10.1042/bj2360313. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hammer C. Isohemagglutinins and preformed natural antibodies in xenogeneic organ transplantation. Transplant Proc. 1987 Dec;19(6):4443–4447. [PubMed] [Google Scholar]
- Karlsson K., Marklund S. L. Heparin-induced release of extracellular superoxide dismutase to human blood plasma. Biochem J. 1987 Feb 15;242(1):55–59. doi: 10.1042/bj2420055. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Karlsson K., Marklund S. L. Plasma clearance of human extracellular-superoxide dismutase C in rabbits. J Clin Invest. 1988 Sep;82(3):762–766. doi: 10.1172/JCI113676. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kato M., Oike Y., Suzuki S., Kimata K. Selective removal of heparan sulfate chains from proteoheparan sulfate with a commercial preparation of heparitinase. Anal Biochem. 1985 Aug 1;148(2):479–484. doi: 10.1016/0003-2697(85)90255-6. [DOI] [PubMed] [Google Scholar]
- Kinsella M. G., Wight T. N. Structural characterization of heparan sulfate proteoglycan subclasses isolated from bovine aortic endothelial cell cultures. Biochemistry. 1988 Mar 22;27(6):2136–2144. doi: 10.1021/bi00406a048. [DOI] [PubMed] [Google Scholar]
- Kissmeyer-Nielsen F., Olsen S., Petersen V. P., Fjeldborg O. Hyperacute rejection of kidney allografts, associated with pre-existing humoral antibodies against donor cells. Lancet. 1966 Sep 24;2(7465):662–665. doi: 10.1016/s0140-6736(66)92829-7. [DOI] [PubMed] [Google Scholar]
- Leung D. Y., Geha R. S., Newburger J. W., Burns J. C., Fiers W., Lapierre L. A., Pober J. S. Two monokines, interleukin 1 and tumor necrosis factor, render cultured vascular endothelial cells susceptible to lysis by antibodies circulating during Kawasaki syndrome. J Exp Med. 1986 Dec 1;164(6):1958–1972. doi: 10.1084/jem.164.6.1958. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Leung D. Y., Moake J. L., Havens P. L., Kim M., Pober J. S. Lytic anti-endothelial cell antibodies in haemolytic-uraemic syndrome. Lancet. 1988 Jul 23;2(8604):183–186. doi: 10.1016/s0140-6736(88)92287-8. [DOI] [PubMed] [Google Scholar]
- Mahowald M. L., Dalmasso A. P., Petzel R. A., Yunis E. J. Linkage relationship of C2 deficiency, HLA and glyoxalase I loci. Vox Sang. 1979;37(6):321–328. doi: 10.1111/j.1423-0410.1979.tb02311.x. [DOI] [PubMed] [Google Scholar]
- Marcum J. A., Atha D. H., Fritze L. M., Nawroth P., Stern D., Rosenberg R. D. Cloned bovine aortic endothelial cells synthesize anticoagulantly active heparan sulfate proteoglycan. J Biol Chem. 1986 Jun 5;261(16):7507–7517. [PubMed] [Google Scholar]
- Matzner Y., Bar-Ner M., Yahalom J., Ishai-Michaeli R., Fuks Z., Vlodavsky I. Degradation of heparan sulfate in the subendothelial extracellular matrix by a readily released heparanase from human neutrophils. Possible role in invasion through basement membranes. J Clin Invest. 1985 Oct;76(4):1306–1313. doi: 10.1172/JCI112104. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nagelkerke J. F., Barto K. P., van Berkel T. J. In vivo and in vitro uptake and degradation of acetylated low density lipoprotein by rat liver endothelial, Kupffer, and parenchymal cells. J Biol Chem. 1983 Oct 25;258(20):12221–12227. [PubMed] [Google Scholar]
- Perper R. J., Najarian J. S. Experimental renal heterotransplantation. I. In widely divergent species. Transplantation. 1966 Jul;4(4):377–388. doi: 10.1097/00007890-196607000-00002. [DOI] [PubMed] [Google Scholar]
- Platt J. L., Brown D. M., Granlund K., Oegema T. R., Klein D. J. Proteoglycan metabolism associated with mouse metanephric development: morphologic and biochemical effects of beta-D-xyloside. Dev Biol. 1987 Oct;123(2):293–306. doi: 10.1016/0012-1606(87)90388-5. [DOI] [PubMed] [Google Scholar]
- Rosenberg J. C., Hawkins E., Rector F. Mechanisms of immunological injury during antibody-mediated hyperacute rejection of renal heterografts. Transplantation. 1971 Feb;11(2):151–157. doi: 10.1097/00007890-197102000-00008. [DOI] [PubMed] [Google Scholar]
- Saku T., Furthmayr H. Characterization of the major heparan sulfate proteoglycan secreted by bovine aortic endothelial cells in culture. Homology to the large molecular weight molecule of basement membranes. J Biol Chem. 1989 Feb 25;264(6):3514–3523. [PubMed] [Google Scholar]
- Zweier J. L., Kuppusamy P., Lutty G. A. Measurement of endothelial cell free radical generation: evidence for a central mechanism of free radical injury in postischemic tissues. Proc Natl Acad Sci U S A. 1988 Jun;85(11):4046–4050. doi: 10.1073/pnas.85.11.4046. [DOI] [PMC free article] [PubMed] [Google Scholar]