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Measurements of tissue content of myeloperoxidase, a constituent of neutrophil azurophil granules and of unsaturated vitamin B12-binding protein from neutrophil-specific granules, have been used to assess intestinal inflammation. This paper reports results of a prospective evaluation of such measurements in serial colonoscopy biopsy specimens from patients with inflammatory bowel disease. Histologic grading of acute inflammation was based on perceived numbers of neutrophil polymorphs in sections from an immediately adjacent biopsy specimen. The mean + 2 SD range for unsaturated vitamin B12-binding protein activity in homogenates of histologically normal specimens was 62 pg mg protein-1. Values increased progressively up to 900 pg mg-1 protein in the most severely inflamed specimens. Unsaturated vitamin B12-binding protein measurements generally distinguished among histologic grades of inflammation, whereas myeloperoxidase activities failed to do this, probably because substantial myeloperoxidase activity was found in uninflamed colonic mucosa, suggesting a non-neutrophil source for this enzyme.

The bacterial chemotactic peptide formyl-met-leu-phe and its radioiodinated analog formyl-met-leu-[125I]tyr are rapidly excreted by the liver into bile following portal or systemic venous infusions in rats or after absorption from the gut lumen. To determine the molecular structural requirements for hepatobiliary excretion of formyl-methionyl peptides, structure-activity studies using portal venous infusions of 24 structural analogs of formyl-met-leu-tyr were performed in rats with biliary cannulae. Hepatic extraction of peptides was studied in vivo using external gamma counting after portal infusion. Efficient hepatobiliary excretion was not restricted to bioactive formyl peptides, but showed a broad specificity for different amino-acylated (formyl, acetyl, propionyl, carbobenzoxy) di- and tripeptides and no requirement for methionine in position one or for a free carboxy terminus. However, nonacylated peptides and an acyl-amino acid showed little excretion. Hepatic extraction of peptide was also related to N-acylation. Hepatic extraction and excretion of N-acyl peptides were also related to hydrophobicity. Thus, the presence of an N-acyl group is the key determinant of biliary excretion of inflammatory bacterial f-met peptides in the rat.

A simple, precise method has been developed for assessing neutrophil secretory responses (release of vitamin B12 binding protein from specific granules) to challenge of aliquots of whole blood with the bacterial chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (fMLP). Dose-response studies performed on blood from normal healthy volunteers showed higher maximal secretory responses in males than females (33.3 +/- SEM 2.2 vs. 27.4 +/- 2.5, P less than .005) a left shift in dose-response curves after feeding compared to fasting (P less than .005), spontaneous up-regulation of responses in blood incubated at 37 degrees C for 1 h, and marked upregulation in response to preincubation with endotoxin. This whole blood challenge method may be used to study neutrophil responses in groups of individuals or patients without the confounding effects of changes in cell responses resulting from cell isolation procedures. The method may also be used as a bioassay for neutrophil-activating factors.