Heme oxygenase isoform expression in cellular and antibody-mediated models of acute inflammation in the rat.
Heme oxygenase (HO) is the rate-limiting enzyme in the catabolism of heme to biliverdin, carbon monoxide (CO), and free iron. The enzyme exists as a constitutive isoform (HO-2) and an inducible isoform (HO-1), which is also a stress protein (HSP32). HO-1 has previously been shown to be associated with the resolution phase of a non-immune model of acute inflammation. In addition, elevation of the enzyme was markedly anti-inflammatory. In the present study, these observations have been extended to two pleural models of immune-driven inflammation in the rat, an immediate type III hypersensitivity (Arthus) reaction and a delayed type IV hypersensitivity reaction. Whilst these models have differing inflammatory mechanisms and time courses, they both showed HO activity to be maximal during the resolution phase. This activity was associated with increases in exudate bilirubin (a breakdown product of biliverdin) and increased expression of HO-1. Immunocytochemical analysis of inflammatory cell smears from the two models showed that HO-1 and HO-2 expression was restricted to mononuclear cells in the type IV hypersensitivity reaction, but included the polymorphonuclear cell population in the type III hypersensitivity reaction. Thus, irrespective of the pathogenesis of the lesion, evidence is accumulating to suggest that HO-1 has a universal role in the resolution of inflammation.
Willis
D
D
Department of Experimental Pathology, Division of Pharmacology, St Bartholomew's and the Royal London School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, UK. dean.willis@ucl.ac.uk
Moore
A R
AR
Willoughby
D A
DA
D000208:Acute Disease; D000818:Animals; D001663:Bilirubin / Q000378:metabolism; D015153:Blotting, Western; D004195:Disease Models, Animal; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D006968:Hypersensitivity, Delayed / Q000201:enzymology; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000473:pathology; D010998:Pleurisy / Q000201:enzymology* / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D012130:Respiratory Hypersensitivity / Q000201:enzymology*; D012710:Serum Albumin, Bovine / Q000276:immunology
D007527:Isoenzymes; D012710:Serum Albumin, Bovine; D006419:Heme Oxygenase (Decyclizing); D001663:Bilirubin