Novel processing pathway for proopiomelanocortin in lymphocytes: endotoxin induction of a new prohormone-cleaving enzyme.
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 C3HeB/FeJ lipopolysaccharide (LPS)-sensitive mice to produce adrenocorticotropin (ACTH) 1-39 and beta-endorphin, whereas LPS induces these lymphocytes to produce ACTH 1-23 to 26 and alpha- or gamma-endorphin. We have proposed that the smaller species of ACTH and endorphin are proteolytic cleavage products from ACTH 1-39 and beta-endorphin. Analysis of C3HeB/FeJ 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 C3H/HeJ (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.
Harbour
D V
DV
Department of Psychiatry and Behavioral Sciences, University of Texas Medical Branch, Galveston 77550.
Smith
E M
EM
Blalock
J E
JE
D000324:Adrenocorticotropic Hormone / Q000096:biosynthesis*; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004731:Endotoxins / Q000494:pharmacology*; D004790:Enzyme Induction; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D001615:beta-Endorphin / Q000096:biosynthesis*
D004731:Endotoxins; D008070:Lipopolysaccharides; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone