MUCIN SECRETION IN INFLAMMATORY BOWEL-DISEASE - COMPARISON OF A MACROPHAGE-DERIVED MUCIN SECRETAGOGUE (MMS-68) TO CONVENTIONAL SECRETAGOGUES

We have described a novel macrophage-derived mucin secretagogue (MMS-6 8) that mediates mucin secretion in colon cancer cell lines and explan ts of normal and inflammatory bowel disease (IBD) mucosa. we compared MMS-68 induced mucin release with other known intestinal mucin secreta gogues in normal colon explants and in the HT-29 colon cancer cell lin e, and to study the effects of MMS-68 on mucin release from inflamed a nd uninflamed ulcerative colitis (UC) and Crohn's disease (CD) mucosa. In normal colonic explants and HT-29 cells, each of the secretagogues including MMS-68-induced mucin release two-to fivefold more than cult ure medium alone. In HT-29 cells, MMS-68 plus leukotriene C-4 (LTC4) i nduced a 50% increase in mucin release over either secretagogue alone, and MMS-68 plus platelet-activating factor (PAF) markedly enhanced mu cin release by eightfold over either secretagogue. In colonic explants from patients with UC and CD, the mucin release in response to MMS-68 was similar to that of normal colonic explants. Likewise, in isolated epithelial cells from CD and UC (whether involved or uninvolved), MMS -68-induced release was similar to that of epithelial cells isolated f rom normal colonic mucosa. The number of MMS-68-producing macrophages was lower in uninflamed UC mucosa compared with inflamed UC mucosa and CD mucosa. The mucin secretagogue activity of MMS-68 is comparable to that of other known secretagogues, and PAF can have a synergistic eff ect on this activity. Whole tissue explants and isolated colonic epith elial cells from patients with IBD respond at least as well as their n ormal counterparts to MMS-68. MMS-68 may play a role in mucin secretio n in normal and inflamed colonic tissue.