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-68) that mediates mucin secretion in colon cancer cell lines and explants of normal and inflammatory bowel disease (IBD) mucosa. We compared MMS-68 induced mucin release with other known intestinal mucin secretagogues in normal colon explants and in the HT-29 colon cancer cell line, and to study the effects of MMS-68 on mucin release from inflamed and 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 culture medium alone. In HT-29 cells, MMS-68 plus leukotriene C4 (LTC4) induced a 50% increase in mucin release over either secretagogue alone, and MMS-68 plus platelet-activating factor (PAF) markedly enhanced mucin 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 from 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 effect on this activity. Whole tissue explants and isolated colonic epithelial cells from patients with IBD respond at least as well as their normal counterparts to MMS-68. MMS-68 may play a role in mucin secretion in normal and inflamed colonic tissue.
Sperber
K
K
Division of Clinical Immunology, Mount Sinai Medical Center, New York, New York, USA.
Shim
J
J
Mehra
M
M
Lin
A
A
George
I
I
Ogata
S
S
Mayer
L
L
Itzkowitz
S
S
D002217:Carbachol / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism*; D003424:Crohn Disease / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007419:Intestinal Secretions; D017997:Leukotriene C4 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D009077:Mucins / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000378:metabolism
D006023:Glycoproteins; C073416:MMS-68 protein, human; D009077:Mucins; D010972:Platelet Activating Factor; D017997:Leukotriene C4; D002217:Carbachol