Hemin-activated macrophages home to the pancreas and protect from acute pancreatitis via heme oxygenase-1 induction.

Abstract

Hemin upregulates heme oxygenase-1 (HO-1), a stress-induced enzyme implicated in protection from a variety of injuries while its related isoform HO-2 is constitutively expressed. The role of hemin or HO-1 in the pancreas and their potential modulation of pancreatic injury are unknown. We show that HO-1 is induced in pancreatitis caused by caerulein and more prominently in severe pancreatitis caused by feeding a choline-deficient diet (CDD). Intraperitoneal hemin administration dramatically increases peritoneal and pancreas macrophages that overexpress HO-1 in association with pancreatic induction of the chemoattractants monocyte chemotactic protein-1 and macrophage inflammatory protein-1alpha but not RANTES or macrophage inflammatory protein-2. Hemin administration before CDD feeding protected 8 of 8 mice from lethality while 7 of 16 controls died. Protection is mediated by HO-1-overexpressing macrophages since hemin-primed macrophages home to the pancreas after transfer to naive mice and protect from CDD-induced pancreatitis. Suppression of hemin-primed peritoneal cell HO-1 using HO-1-specific small interfering RNA prior to cell transfer abolishes protection from CDD-induced pancreatitis. Similarly, hemin pretreatment in caerulein-induced pancreatitis reduces serum amylase and lipase, decreases pancreatic trypsin generation, and protects from lung injury. Therefore, hemin-like compounds or hemin-activated macrophages may offer novel therapeutic approaches for preventing acute pancreatitis and its pulmonary complication via upregulation of HO-1.

• Authors: Ikuo Nakamichi, Aida Habtezion, Bihui Zhong, Christopher H Contag, Eugene C Butcher, M Bishr Omary
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 115 Issue 11 Pg. 3007-14 (Nov 2005) ISSN: 0021-9738 [Print] United States
• PMID: 16239966 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Hemin
• Heme Oxygenase-1

Topics

• Acute Disease
• Animals
• Cell Movement (physiology)
• Disease Models, Animal
• Enzyme Induction
• Female
• Heme Oxygenase-1 (biosynthesis, physiology)
• Hemin (physiology)
• Macrophages (enzymology, pathology)
• Macrophages, Peritoneal (enzymology, pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Transgenic
• Pancreas (enzymology, pathology)
• Pancreatitis (enzymology, pathology)