Bacterial chemotactic peptides (F-met-oligopeptides) are secreted by several species of commensal enteric bacteria and can be assayed by bioassay techniques in human colonic luminal fluid. We have previously demonstrated intestinal absorption and enterohepatic circulation of radiolabelled F-met peptides introduced into rat colon, and an eightfold increase in absorption and biliary excretion in rats with experimental colitis. This paper describes the application of a radio-immunoassay to measurements of formyl oligopeptides in human faecal dialysates, colonic and systemic venous blood and bile. All samples were fractionated by reverse-phase high performance liquid chromatography (HPLC) prior to assay. Immunoreactivity was found in faecal dialysates (5-700 nmol/L F-met-leu-phe equivalents) and bile samples (3-150 nmol/L) from normal subjects. After HPLC fractionation, up to five distinct peaks of immunoreactivity were identified. One of these co-chromatographed with authentic F-met-leu-phe; the others probably represented either closely related peptides or peptides of different chain lengths originating from the same F-met-leu-phe precursor protein. Colonic venous blood from two patients with ulcerative colitis contained immunoreactive peptide (10-30 nmol/L) and substantial immunoreactivity was found in ileostomy fluid and bile from two patients with primary sclerosing cholangitis. These results suggest the presence of an enterohepatic circulation of bacterial F-met oligopeptides in man and provide a basis for studies of the role of such pro-inflammatory peptides in patients with inflammatory bowel disease and associated hepatobiliary disorders.

No abstract

beta cells in the human fetal pancreas are immature in that they release little or no insulin in response to nutrients, such as glucose. The aim of this study was to examine further the immaturity of these cells, specifically regarding the storage and release of the precursor of insulin, proinsulin. Explants of human fetal pancreas were cultured in vitro for 3 weeks. Levels of proinsulin remained relatively constant throughout at 0.04 +/- 0.002 (S.E.M.) pmol/mg per day with a molar ratio of proinsulin to insulin of 2.2 +/- 0.11%. This low ratio was slightly greater than that observed in culture medium conditioned by adult human islets (0.3 +/- 0.1%), but similar to that found in acid-ethanol extracts of cultured explants (1.4 +/- 0.3%). Passaging of human fetal pancreas for 3 months in diabetic nude mice, which should have caused some maturation of the fetal beta cell, did not change the proportion of proinsulin present. Culture of explants in the presence of 12-O-tetra-decanoylphorbol-13-acetate resulted in some inhibition of proinsulin release, but much less than that for insulin, so that the molar ratio increased to 15.4 +/- 1.6% from the control 3.5 +/- 0.3%. Static stimulation of cultured explants with 10 mmol Ca2+/l, 10 mmol theophylline/l, and these two agents together caused 15-, 4- and 10-fold enhancement respectively of proinsulin release; glucose, leucine, arginine and KCl had no effect. In contrast, all these agents caused significant insulin release, the last four to a much smaller extent (less than or equal to three fold) than the first three (10-, 19- and 65-fold respectively).(ABSTRACT TRUNCATED AT 250 WORDS)