An immunologic approach to induction of epidermal growth factor deficiency: induction and characterization of autoantibodies to epidermal growth factor in rats
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
An immunologic approach to induction of epidermal growth factor deficiency : induction and characterization of autoantibodies to epidermal growth factor in rats. / Raaberg, Lasse; Nexø, Ebba; Poulsen, Steen Seier; Jørgensen, P E.
I: Pediatric Research, Bind 37, Nr. 2, 02.1995, s. 169-74.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - An immunologic approach to induction of epidermal growth factor deficiency
T2 - induction and characterization of autoantibodies to epidermal growth factor in rats
AU - Raaberg, Lasse
AU - Nexø, Ebba
AU - Poulsen, Steen Seier
AU - Jørgensen, P E
PY - 1995/2
Y1 - 1995/2
N2 - 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.
AB - 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.
KW - Animals
KW - Antigen-Antibody Complex
KW - Autoantibodies
KW - Duodenum
KW - Epidermal Growth Factor
KW - Female
KW - Immunization
KW - Immunoenzyme Techniques
KW - Liver
KW - Lung
KW - Rats
KW - Rats, Wistar
KW - Receptor, Epidermal Growth Factor
KW - Saliva
KW - Spleen
KW - Submandibular Gland
KW - Urine
U2 - 10.1203/00006450-199502000-00008
DO - 10.1203/00006450-199502000-00008
M3 - Journal article
C2 - 7731753
VL - 37
SP - 169
EP - 174
JO - Pediatric Research
JF - Pediatric Research
SN - 0031-3998
IS - 2
ER -
ID: 47487134