Novel processing pathway for proopiomelanocortin in lymphocytes: Endotoxin induction of a new prohormone-Cleaving enzyme
✍ Scribed by D. V. Harbour; E. M. Smith; J. E. Blalock
- Book ID
- 102911873
- Publisher
- John Wiley and Sons
- Year
- 1987
- Tongue
- English
- Weight
- 703 KB
- Volume
- 18
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
We have discovered that the immune system processes proopiomelanocortin (POMC) products differently depending on the stimulus for induction. We have shown that corticotropin-releasing factor (CRF) induces the lymphocytes from C3HeBlFe.J lipopolysaccharide (LPS)-sensitive mice to produce adrenocorticotropin (ACTH) 1-39 and &endorphin, whereas LPS induces these lymphocytes to produce ACTH 1- 23 to 26 and a-or y-endorphin. We have proposed that the smaller species of ACTH and endorphin are proteolytic cleavage products from ACTH 1-39 and pendorphin. Analysis of C3HeBlFeJ LPS-treatment B lymphocyte lysates showed an enzymatic activity at pH 5 but not pH 7 that cleaved ACTH 1-39 into a smaller ACTH 1-23 to 26. The B lymphocytes from C3HlHe.J (LPS-resistant) mice expressed but did not process proopiomelanocortin after LPS or CRF treatment, nor did their B cells express the aforementioned enzymatic activity. Taken together, these data suggest a unique processing pathway in LPS-treated B lymphocytes and one in which immunoreactive (ir)-endorphins may play a role in the pathophysiology of endotoxic shock.