Disappearance of 125I-labelled myelin basic protein from blood circulation and its degradation and accumulation in various tissues in rats

Abstract

Following acute central nervous system myelin injury, immunoreactive myelin basic protein (MBP) has been detected in the cerebrospinal fluid, blood and urine. In order to clarify the fate of MBP in the circulation, distribution and degradation of intravenously injected bovine MBP was followed in anaestethized rats for 5 to 240 min by using 125I-labelled MBP. Five minutes after injection of a dose of 60–400 ng of MBP, 44% of the label was recovered in the liver, 6.3% in the kidneys, 4.7% in the lungs and 15% in the blood circulation, the corresponding figures at a dose of 0.8 mg being 51, 7.4, 0.8 and 22%. The liver discarded the label fastest, 3% of the dose remaining 4 h after injection. The amount of label in urine increased simultaneously, the recovery at 4 h being 5.5% of the lower and 4.2% of the higher MBP dose. The percentage of total dose of the label per gram of tissue at 5 min (= distribution percentage, DP-5) was 3–4% in the liver and kidney and 1.6% in the spleen. The label content in the pancreas was increased at 15–60 min, compared to the DP-5 of 0.3% with a two-fold maximum at 30 min. The duodenum concentrated MBP in a similar manner as the pancreas but not as extensively. The DP-5 of 0.1% in the thymus was concentrated two-fold with a maximum at 60 min. A slight concentration occured in the heart. The DP-5 of 0.03% in muscle, testis and brain was concentrated 3-fold at 60 min, 3.6-fold at 60–240 min and 2-fold at 30–60 min in the aforementioned tissues, respectively. In spite of degradation of the label in tissues, the distribution of high molecular weight (HMW = TCA-precipitable) MBP was similar. Other experiments showed that the kidney, lung and duodenum contained most of the HMW MBP at 20 h. Upon continuous release of MBP, the pancrease, thymus, duodenum, muscle and testis would thus cumulatively concentrate MBP, and the kidney, lung and duodenum would be quantitatively most affected. MBP was previously shown to enter into cells of pancreative islets and to stimulate insulin and glucagon release. It could have biological effects in other tissues as well. These effects could explain some peripheral symptoms present in neurological disorders.