Heme oxygenase-1 is induced in peripheral blood mononuclear cells of patients with acute pancreatitis: a potential therapeutic target.
Heme oxygenase-1 (HO-1) induction by hemin or Panhematin protects against experimental pancreatitis. As a preclinical first step toward determining whether HO-1 upregulation is a viable target in acute pancreatitis (AP) patients, we tested the hypothesis that HO-1 expression in peripheral blood mononuclear cell (PBMC) subsets of hospitalized patients with mild AP is upregulated then normalizes upon recovery and that cells from AP patients have the potential to upregulate their HO-1 ex vivo if exposed to Panhematin. PBMCs were isolated on days 1 and 3 of hospitalization from the blood of 18 AP patients, and PMBC HO-1 levels were compared with PMBCs of 15 hospitalized controls (HC) and 7 volunteer healthy controls (VC). On day 1 of hospitalization, AP patients compared with VCs had higher HO-1 expression in monocytes and neutrophils. Notably, AP monocyte HO-1 levels decreased significantly upon recovery. Panhematin induced HO-1 in ex vivo cultured AP PBMCs more readily than in HC or VC PBMCs. Furthermore, PBMCs from acutely ill AP patients on day 1 were more responsive to HO-1 induction compared with day 3 upon recovery. Similarly, mouse splenocytes had enhanced HO-1 inducibility as their pancreatitis progressed from mild to severe. In conclusion, AP leads to reversible PBMC HO-1 upregulation that is associated with clinical improvement and involves primarily monocytes. Leukocytes from AP patients or mice with AP are primed for HO-1 induction by Panhematin, which suggests that Panhematin could offer a therapeutic benefit.
Habtezion
Aida
A
Stanford Univ. School of Medicine, Dept. of Medicine, Division of Gastroenterology & Hepatology, 300 Pasteur Dr., Stanford, CA 94305, USA. aidah@stanford.edu
Kwan
Raymond
R
Yang
Alice L
AL
Morgan
Maureen E
ME
Akhtar
Ehsaan
E
Wanaski
Stephen P
SP
Collins
Stephen D
SD
Butcher
Eugene C
EC
Kamal
Ahmad
A
Omary
M Bishr
MB
D000328:Adult; D000818:Animals; D001773:Blood Cells / Q000201:enzymology; D004790:Enzyme Induction; D005260:Female; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D006427:Hemin / Q000494:pharmacology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D010195:Pancreatitis / Q000201:enzymology* / Q000235:genetics; D015854:Up-Regulation
D006427:Hemin; D051547:Heme Oxygenase-1