An immunologic approach to induction of epidermal growth factor deficiency: induction and characterization of autoantibodies to epidermal growth factor in rats.
(1995)
Journal - Pediatric research (UNITED STATES )
Abstract :
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.
| ISSN : | 0031-3998 |
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| Mesh Heading : | Animals Antigen-Antibody Complex Autoantibodies Duodenum Epidermal Growth Factor Female Immunization Immunoenzyme Techniques Liver Lung Rats Rats, Wistar Receptor, Epidermal Growth Factor Saliva Spleen Submandibular Gland Urine metabolism biosynthesis chemistry ultrastructure immunology physiology chemistry ultrastructure chemistry ultrastructure antagonists & inhibitors chemistry chemistry ultrastructure chemistry ultrastructure chemistry |
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| Mesh Heading Relevant : | immunology antagonists & inhibitors |
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Fetal effects of epidermal growth factor deficiency induced in rats by autoantibodies against epidermal growth factor.
(1995)
Journal - Pediatric research (UNITED STATES )
Abstract :
We have used rats with epidermal growth factor (EGF) autoantibodies to study the role of EGF deficiency during perinatal development. The study was focused on organs known to contain EGF or its receptor. Compared with controls, the offspring of autoimmune rats had a higher perinatal mortality and a lower birth weight. The weight of the lungs was particularly low in the offspring of EGF-immunized rats, and morphologically the lungs from the surviving pups seemed atelectatic and had alveolar duct dilatation, which indicates mild respiratory distress syndrome. Judged from immunohistochemical studies, the amount of surfactant protein-A was decreased, suggesting a delayed lung maturation. The offspring of EGF-immunized rats had dry and wrinkled skin. The skin was thin and the hair follicles were immature. This suggests a role for EGF in the growth and development of the skin. The liver/body weight ratio was lower in pups from EGF-immunized rats. This difference was, however, not significant (p = 0.07), but flow cytometric analyses showed a significantly lower proportion of the liver cells from newborn EGF-deficient pups to be in S-phase and indicated that these cells were larger than liver cells from controls. To study possible alterations in EGF binding, 125I-EGF was injected i.v. in newborn rats. 125I-EGF bound in all the organs investigated. The binding is listed in decreasing order: liver, gut, skin, kidney, and lungs. In the pups from EGF-immunized rats, the lungs and the skin bound a significantly higher amount than the controls.(ABSTRACT TRUNCATED AT 250 WORDS)
| ISSN : | 0031-3998 |
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| Mesh Heading : | Abnormalities, Multiple Animals Autoantibodies Birth Weight Digestive System Embryonic and Fetal Development Epidermal Growth Factor Female Immunization Liver Lung Pregnancy Pregnancy Complications Pulmonary Atelectasis Rats Rats, Wistar Skin biosynthesis embryology immunology physiology embryology etiology |
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| Mesh Heading Relevant : | etiology immunology physiology antagonists & inhibitors embryology embryology immunology embryology |
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