DIFFERENTIAL EXCRETION OF LEUKOCYTE GRANULE COMPONENTS IN INFLAMMATORY BOWEL-DISEASE - IMPLICATIONS FOR PATHOGENESIS

1. Faecal excretion of the leucocyte primary granule component, myelop eroxidase, and of the secondary granule component, lactoferrin, were c ompared in inflammatory bowel disease and infective diarrhoea. 2. Faec al lactoferrin correlated with faecal myeloperoxidase in both inflamma tory bowel disease (P = 0.0018; n = 32) and infective diarrhoea (P = 0 .00013; n = 37), but inflammatory bowel disease was associated with a much higher faecal excretion of lactoferrin but lower excretion of mye loperoxidase than infective diarrhoea, As a consequence, the median ra tio of lactoferrin/myeloperoxidase excretion (both expressed as ng/mg of protein) for inflammatory bowel disease was 7.5 (range 3.5-21.3) wi th similar values for ulcerative colitis (n = 18) and Crohn's disease (n = 14) compared with only 0.9 (range 0.4-2.3; P < 0.0001) for infect ive diarrhoea, In inflammatory bowel disease faecal lactoferrin and my eloperoxidase excretion remained increased even in clinical remission. 3. In subsequent immunohistochemical studies to assess the possible e xplanation for these findings, lactoferrin and myeloperoxidase were de monstrated within crypt abscesses and surface mucus, both in inflammat ory bowel and in infective diarrhoea mucosal samples, There was a slig ht increase in the number of lactoferrin-containing cells in the mucos al samples from ulcerative colitis and in the submucosa of samples fro m Crohn's disease compared with infective diarrhoea, but these changes were not sufficient to account for the marked increase in faecal lact oferrin excretion in inflammatory bowel disease. 4. In all mucosal sam ples, including those from normal mucosa, lactoferrin was also shown t o be contained within mast cells. 5. These results could best be expla ined by a different mechanism for leucocyte activation in inflammatory bowel disease compared wvith infective diarrhoea, and are compatible with selective secretion of secondary granule components, which includ e lactoferrin but not myeloperoxidase, as a result of leucocyte activa tion by N-formylated bacterial peptides in inflammatory bowel disease.