An immunologic approach to induction of epidermal growth factor deficiency: induction and characterization of autoantibodies to epidermal growth factor in rats.
Epidermal growth factor (EGF) in pharmacologic doses is able to induce growth and development in the fetus and the newborn. To investigate the opposite situation, the effects of insufficient amounts of EGF during development, we wanted to establish an in vivo model with a state of EGF deficiency. This was attempted by induction of autoimmunity to EGF in rats. Twenty rats were immunized with EGF. Fifteen of these developed autoantibodies against EGF, which, as judged by Scatchard analysis, had a median apparent affinity constant of 14 x 10(9) L/mol and a median concentration of binding sites of 20 x 10(-9) mol/L. The antibodies recognized purified EGF from the submandibular glands (6 kD) and from urine (45 kD) and further native EGF in saliva and urine. The cross-reactivity toward transforming growth factor-alpha was below 3%. Binding of EGF by antibodies inhibited its binding to the EGF-receptor by approximately 97% in vitro. Investigation of in vivo metabolism of antibody-bound 125I-EGF confirmed these results, that is, the antibodies were able to inactivate EGF. The adult rats were unaffected by the induction and presence of autoantibodies, and the EGF-containing organs did not show any histologic signs of inflammation or tissue damage. Furthermore, as judged by immunohistochemistry, no major changes in the distribution and tissue concentration of EGF were seen in the adult rat. These results show that it is possible to induce homologous antibodies that can inhibit the binding of EGF to its receptor and further suggest that circulatory EGF is of no physiologic importance in the healthy, adult rat.
Raaberg
L
L
Institute of Medical Anatomy, Panum Institute, Copenhagen, Denmark.
Nexø
E
E
Poulsen
S S
SS
Jørgensen
P E
PE
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology*; D004386:Duodenum / Q000737:chemistry / Q000648:ultrastructure; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D007114:Immunization; D007124:Immunoenzyme Techniques; D008099:Liver / Q000737:chemistry / Q000648:ultrastructure; D008168:Lung / Q000737:chemistry / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D012463:Saliva / Q000737:chemistry; D013154:Spleen / Q000737:chemistry / Q000648:ultrastructure; D013363:Submandibular Gland / Q000737:chemistry / Q000648:ultrastructure; D014556:Urine / Q000737:chemistry
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D004815:Epidermal Growth Factor; D066246:ErbB Receptors