Abstract
1. The effects of normal rabbit serum and of rabbit antiserum to whole foetal mouse tissues, on the isolated limb bones of late foetal mice were studied in organ culture, and the influence of hydrocortisone on these effects was investigated. 2. Unheated normal serum caused slight loss of metachromatic material from the cartilage matrix, and some resorption of both cartilage and bone. 3. In unheated antiserum to foetal mouse tissues, the terminal cartilage was smaller and less metachromatic than in paired controls in normal serum, while osteoclasis was so intense that in many explants the bone had almost disappeared. The amount of necrosis varied with different batches of antiserum. 4. The changes produced by normal serum and antiserum could be largely prevented by heating the sera to 57°C for 45 minutes. 5. The effects could also be inhibited by the addition of hydrocortisone to the unheated sera; as little as 0.1 µg hydrocortisone per ml of medium had a well marked protective action. 6. It is suggested that (a) unheated antiserum causes a release of lysosomal enzymes with consequent breakdown of intercellular material, (b) this release is due to an indirect action on the lysosome via an increased permeability of the cell membrane, (c) hydrocortisone does not affect the antigen-antibody reaction, but inhibits the autolytic changes that normally follow this reaction, possibly by stabilising both the lysosomal and cell membranes.
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Selected References
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- BIGGERS J. D., GWATKIN R. B., HEYNER S. Growth of embryonic avian and mammalian tibiae on a relatively simple chemically defined medium. Exp Cell Res. 1961 Oct;25:41–58. doi: 10.1016/0014-4827(61)90305-6. [DOI] [PubMed] [Google Scholar]
- BITENSKY L. CYTOTOXIC ACTION OF ANTIBODIES. Br Med Bull. 1963 Sep;19:241–244. doi: 10.1093/oxfordjournals.bmb.a070064. [DOI] [PubMed] [Google Scholar]
- DINGLE J. T. Aetiological factors in the collagen diseases. Lysosomal enzymes and the degradation of cartilage matrix. Proc R Soc Med. 1962 Feb;55:109–111. [PubMed] [Google Scholar]
- DINGLE J. T., LUCY J. A., FELL H. B. Studies on the mode of action of excess of vitamin A. 1. Effect of excess of vitamin A on the metabolism and composition of embryonic chick-limb cartilage grown in organ culture. Biochem J. 1961 Jun;79:497–500. doi: 10.1042/bj0790497. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DINGLE J. T. Studies on the mode of action of excess of vitamin A. 3. Release of a bound protease by the action of vitamin A. Biochem J. 1961 Jun;79:509–512. doi: 10.1042/bj0790509. [DOI] [PMC free article] [PubMed] [Google Scholar]
- FELL H. B., DINGLE J. T. Studies on the mode of action of excess of vitamin A. 6. Lysosomal protease and the degradation of cartilage matrix. Biochem J. 1963 May;87:403–408. doi: 10.1042/bj0870403. [DOI] [PMC free article] [PubMed] [Google Scholar]
- FELL H. B., MELLANBY E. The effect of hypervitaminosis A on embryonic limb bones cultivated in vitro. J Physiol. 1952 Mar;116(3):320–349. doi: 10.1113/jphysiol.1952.sp004708. [DOI] [PMC free article] [PubMed] [Google Scholar]
- FELL H. B., THOMAS L. Comparison of the effects of papain and vitamin A on cartilage. II. The effects on organ cultures of embryonic skeletal tissue. J Exp Med. 1960 May 1;111:719–744. doi: 10.1084/jem.111.5.719. [DOI] [PMC free article] [PubMed] [Google Scholar]
- FELL H. B., THOMAS L. The influence of hydrocortisone on the action of excess vitamin A on limb bone rudiments in culture. J Exp Med. 1961 Sep 1;114:343–362. doi: 10.1084/jem.114.3.343. [DOI] [PMC free article] [PubMed] [Google Scholar]
- GIANETTO R., DE DUVE C. Tissue fractionation studies. 4. Comparative study of the binding of acid phosphatase, beta-glucuronidase and cathepsin by rat-liver particles. Biochem J. 1955 Mar;59(3):433–438. doi: 10.1042/bj0590433. [DOI] [PMC free article] [PubMed] [Google Scholar]
- JANOFF A., WEISSMANN G., ZWEIOFACH B. W., THOMAS L. Pathogenesis of experimental shock. IV. Studies on lysosomes in normal and tolerant animals subjected to lethal trauma and endotoxemia. J Exp Med. 1962 Oct 1;116:451–466. doi: 10.1084/jem.116.4.451. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LUCY J. A., DINGLE J. T., FELL H. B. Studies on the mode of action of excess of vitamin A. 2. A possible role of intracellular proteases in the degradation of cartilage matrix. Biochem J. 1961 Jun;79:500–508. doi: 10.1042/bj0790500. [DOI] [PMC free article] [PubMed] [Google Scholar]
- ROSENAU W., MOON H. D. The inhibitory effect of hydrocortisone on lysis of homologous cells by lymphocytes in vitro. J Immunol. 1962 Sep;89:422–426. [PubMed] [Google Scholar]
- WEISS L., DINGLE J. T. LYSOSOMAL ACTIVATION IN RELATION TO CONNECTIVE TISSUE DISEASE. Ann Rheum Dis. 1964 Jan;23:57–63. doi: 10.1136/ard.23.1.57. [DOI] [PMC free article] [PubMed] [Google Scholar]
- WEISSMANN G., DINGLE J. Release of lysosomal protease by ultraviolet irradiation and inhibition by hydrocortisone. Exp Cell Res. 1961 Oct;25:207–210. doi: 10.1016/0014-4827(61)90328-7. [DOI] [PubMed] [Google Scholar]
- WEISSMANN G., FELL H. B. The effect of hydrocortisone on the response of fetal rat skin in culture to ultraviolet irradiation. J Exp Med. 1962 Sep 1;116:365–380. doi: 10.1084/jem.116.3.365. [DOI] [PMC free article] [PubMed] [Google Scholar]
- WEISSMANN G., THOMAS L. Studies on lysosomes. I. The effects of endotoxin, endotoxin tolerance, and cortisone on the release of acid hydrolases from a granular fraction of rabbit liver. J Exp Med. 1962 Oct 1;116:433–450. doi: 10.1084/jem.116.4.433. [DOI] [PMC free article] [PubMed] [Google Scholar]