Apoptosis induction in vivo and fate of apoptotic material in the colon of the guinea pig.

Short-chain fatty acids (SCFA) in particular butyrate are regarded as an energy source acting in beneficial, protective manner on the colonic mucosa. Previous investigations showed that the colonic mucosa bathed in Ussing chamber with a solution lacking butyrate induced massive apoptosis of epithelial cells. The apoptotic material (bodies and cells) was shed at the mucosa surface. In the present study we aimed to investigate the effects caused in vivo on the colonic mucosa by the absence of butyrate. For this purpose the colon of guinea pigs was perfused in situ with solutions either containing or lacking butyrate. The results show that within 2h of perfusion without butyrate a large amount of epithelial cells underwent apoptosis as in the in vitro experiments. However, apoptotic material instead to be extruded at the epithelial surface accumulates into the intercellular spaces from which it becomes removed by an unusual high number of macrophages. These, engorged with phagocytozed material, lie assembled in a layer below the epithelium. Similar alterations have not been observed after perfusion in the presence of butyrate. The results suggest that this SCFA may protect the colonic mucosa in that it prevents apoptosis. The alterations occurring during 2h of its absence allow to assume that a protracted butyrate deprivation may lead to a breakdown of the integrity of the mucosa thus influencing differently the activity of the macrophages.