Investigation of the expression of IL-1beta converting enzyme and apoptosis in normal and inflammatory bowel disease (IBD) mucosal macrophages.
Activated mucosal macrophages are derived from circulating monocytes and appear to play a major role in the pathogenesis of IBD. We have recently shown that IBD, but not normal, mucosal macrophages express the active form of IL-1beta converting enzyme (ICE) and are therefore capable of releasing mature IL-1beta. ICE expression by other mucosal cell types is unknown. Active ICE expression has also been implicated in apoptosis. The aim of this study was to investigate ICE expression (using an antibody that recognizes both active and precursor forms) in normal and IBD mucosa and to determine whether ICE-expressing macrophages are undergoing apoptosis. Normal and active IBD mucosal cells, in tissue sections and after isolation, were studied by immunohistochemistry and flow cytometry. In the mucosa, macrophages were the predominant ICE-expressing cell type. In contrast to normal, most IBD mucosal macrophages expressed ICE. Of IBD colonic macrophages 11.8 +/- 3.2%, and of normal colonic macrophages 6.6 +/- 0.6% expressed Apo2.7, a marker for apoptotic cells. Similar data were obtained when annexin V was used to identify cells undergoing apoptosis. DNA fluorescence flow cytometric analysis of normal and IBD lamina propria cells showed the presence of only small hypodiploid DNA peaks. We conclude that in the human intestinal mucosa, macrophages are the predominant ICE-expressing cell type. Expression of the active form of ICE and macrophage apoptosis are not interdependent. One mechanism of loss of resident macrophages from normal mucosa and of recruited macrophages from IBD mucosa is by apoptosis.
McAlindon
M E
ME
Division of Gastroenterology, University Hospital, Queen's Medical Centre, Nottingham, UK.
Galvin
A
A
McKaig
B
B
Gray
T
T
Sewell
H F
HF
Mahida
Y R
YR
D017209:Apoptosis; D020170:Caspase 1 / Q000378:metabolism*; D003106:Colon / Q000201:enzymology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000201:enzymology* / Q000473:pathology; D007413:Intestinal Mucosa / Q000201:enzymology; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008264:Macrophages / Q000201:enzymology* / Q000473:pathology
D018950:Lipopolysaccharide Receptors; D020170:Caspase 1