Investigation of the expression of IL-1 beta converting enzyme and apoptosis in normal and inflammatory bowel disease (IBD) mucosal macrophages

Activated mucosal macrophages are derived from circulating monocytes and ap pear to play a major role in the pathogenesis of IBD. We have recently show n that IBD, but not normal, mucosal macrophages express the active form of IL-1 beta converting enzyme (ICE) and are therefore capable of releasing ma ture IL-1 beta. ICE expression by other mucosal cell types is unknown. Acti ve ICE expression has also been implicated in apoptosis. The aim of this st udy was to investigate ICE expression (using an antibody that recognizes bo th active and precursor forms) in normal and IBD mucosa and to determine wh ether ICE-expressing macrophages are undergoing apoptosis. Normal and activ e IBD mucosal cells, in tissue sections and after isolation, were studied b y immunohistochemistry and flow cytometry. In the mucosa, macrophages were the predominant ICE-expressing cell type. In contrast to normal, most IBD m ucosal 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 analy sis of normal and IBD lamina propria cells showed the presence of only smal l hypodiploid DNA peaks. We conclude that in the human intestinal mucosa, m acrophages are the predominant ICE-expressing cell type. Expression of the active form of ICE and macrophage apoptosis are not interdependent. One mec hanism of loss of resident macrophages from normal mucosa and of recruited macrophages from IBD mucosa is by apoptosis.