Developmental regulation of human truncated nerve growth factor receptor.
Monoclonal antibodies (designated XIF1 and IIIG5) recognizing distinct epitopes of the human truncated nerve growth factor receptor (NGF-Rt) were used in a two-site radiometric immunosorbent assay to monitor levels of NGF-Rt in human urine as a function of age. Urine samples were collected from 70 neurologically normal subjects ranging in age from 1 month to 68 years. By using this sensitive two-site radiometric immunosorbent assay, NGF-Rt levels were found to be highest in urine from 1-month old subjects. By 2.5 months, NGF-Rt values were half of those seen at 1 month and decreased more gradually between 0.5 and 15 years. Between 15 and 68 years, urine NGF-Rt levels were relatively constant at 5% of 1-month values. No evidence for diurnal variation of adult NGF-Rt was apparent. Pregnant women in their third trimester showed significantly elevated urine NGF-Rt values compared with age-matched normals. Affinity labeling of NGF-Rt with 125I-NGF followed by immunoprecipitation with ME20.4-IgG and gel autoradiography indicated that neonatal urine contained high amounts of truncated receptor (Mr = 50 kd); decreasingly lower amounts of NGF-Rt were observed on gel autoradiograms with development, indicating that the two-site radiometric immunosorbent assay correlated well with the affinity labeling technique for measuring NGF-Rt. NGF-Rt in urines from 1-month-old and 36-year-old subjects showed no differences in affinities for NGF or for the monoclonal antibody IIIG5. These data show that NGF-Rt is developmentally regulated in human urine, and are discussed in relation to the development and maturation of the peripheral nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)
DiStefano
P S
PS
Neuroscience Research Division, Abbott Laboratories, Abbott Park, IL 60064.
Clagett-Dame
M
M
Chelsea
D M
DM
Loy
R
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D000911:Antibodies, Monoclonal; D001345:Autoradiography; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D006801:Humans; D015592:Immunoradiometric Assay / Q000379:methods; D007223:Infant; D007231:Infant, Newborn; D007700:Kinetics; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000378:metabolism; D010525:Peripheral Nerves / Q000254:growth & development; D011233:Precipitin Tests; D011956:Receptors, Cell Surface / Q000652:urine*; D017475:Receptors, Nerve Growth Factor; D012711:Serum Albumin, Radio-Iodinated
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D009414:Nerve Growth Factors; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; D012711:Serum Albumin, Radio-Iodinated