Abstract
The serum disappearance, metabolic clearance and whole body catabolism of homologous immunoglobulin fragments were studied in rats. The rapid disappearance of Fab fragments from serum in normal animals was no longer present after nephrectomy. In contrast, the serum disappearance curve of Fc fragments was not altered by nephrectomy. The results of three different experiments, however, indicated that similar to Fab fragments, some Fc fragments underwent filtration and degradation in the kidneys. First, the amount of intact Fc fragments excreted in the first day after injection increased from 6% of the injected dose in normal rats to 17% in rats pretreated with sodium maleate. Secondly, nephrectomy eliminated the rapid phase of whole body catabolism of inected Fc fragments. Thirdly, auto-radiographic studies showed localization of Fc fragments in the renal proximal tubule cells in the first 3 hr after injection. An identical localization was seen with Fab fragments. These results support the conclusion that removal from circulation by glomerular filtration and subsequent reabsorption and degradation in proximal tubule cells represent the major mechanism for catabolism of Fab fragments. Although some Fc fragments undergo the same fate, most injected Fc fragments equilibrate with unknown sites where they are possibly bound and made unavailable for filtration in the kidneys.
Full text
PDF
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- FAHEY J. L., ROBINSON A. G. FACTORS CONTROLLING SERUM GAMMA-GLOBULIN CONCENTRATION. J Exp Med. 1963 Nov 1;118:845–868. doi: 10.1084/jem.118.5.845. [DOI] [PMC free article] [PubMed] [Google Scholar]
- HELMKAMP R. W., GOODLAND R. L., BALE W. F., SPAR I. L., MUTSCHLER L. E. High specific activity iodination of gamma-globulin with iodine-131 monochloride. Cancer Res. 1960 Nov;20:1495–1500. [PubMed] [Google Scholar]
- Heinemann H. O., Maack T. M., Sherman R. L. Proteinuria. Am J Med. 1974 Jan;56(1):71–82. doi: 10.1016/0002-9343(74)90752-9. [DOI] [PubMed] [Google Scholar]
- Maunsbach A. B. Absorption of I-125-labeled homologous albumin by rat kidney proximal tubule cells. A study of microperfused single proximal tubules by electron microscopic autoradiography and histochemistry. J Ultrastruct Res. 1966 Jun;15(3):197–241. doi: 10.1016/s0022-5320(66)80108-9. [DOI] [PubMed] [Google Scholar]
- Mogielnicki R. P., Waldmann T. A., Strober W. Renal handling of low molecular weight proteins. I. L-Chain metabolism in experimental renal disease. J Clin Invest. 1971 Apr;50(4):901–909. doi: 10.1172/JCI106562. [DOI] [PMC free article] [PubMed] [Google Scholar]
- PORTER R. R. The hydrolysis of rabbit y-globulin and antibodies with crystalline papain. Biochem J. 1959 Sep;73:119–126. doi: 10.1042/bj0730119. [DOI] [PMC free article] [PubMed] [Google Scholar]
- SPIEGELBERG H. L., WEIGLE W. O. THE CATABOLISM OF HOMOLOGOUS AND HETEROLOGOUS 7S GAMMA GLOBULIN FRAGMENTS. J Exp Med. 1965 Mar 1;121:323–338. doi: 10.1084/jem.121.3.323. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Spiegelberg H. L., Fishkin B. G. The catabolism of human G immunoglobulins of different heavy chain subclasses. 3. The catabolism of heavy chain disease proteins and of Fc fragments of myeloma proteins. Clin Exp Immunol. 1972 Apr;10(4):599–607. [PMC free article] [PubMed] [Google Scholar]
- Wochner R. D., Strober W., Waldmann T. A. The role of the kidney in the catabolism of Bence Jones proteins and immunoglobulin fragments. J Exp Med. 1967 Aug 1;126(2):207–221. doi: 10.1084/jem.126.2.207. [DOI] [PMC free article] [PubMed] [Google Scholar]