EVIDENCE FOR A CD14(-DISEASE MUCOSA-IMPLICATIONS FOR PATHOGENESIS() POPULATION OF MONOCYTES IN INFLAMMATORY BOWEL)

Lipopolysaccharide (LPS) is abundant in the intestinal lumen. CD14 is the receptor for the LPS-LPS binding protein complex, and its presence on mononuclear phagocytes allows cell activation by pg/ml concentrati ons of LPS. We have shown that the recently recruited blood monocyte i n inflammatory bowel disease mucosa is CD14(+). This study examined th e expression of CD14 on macrophages in inflamed (n = 13) and uninflame d (n = 7) intestine by immunohistochemistry, and on disaggregated lami na propria mononuclear cells (12 from inflamed, 17 from uninflamed int estine) and peripheral blood mononuclear cells (n = 26) by flow cytome try, using a panel of three MoAbs directed against CD14. Immunohistoch emistry revealed that 3.7% of macrophages in uninflamed intestine were CD14(+), while 25.1% of macrophages in active inflammatory bowel dise ase expressed CD14 (P < 0.02). Flow cytometry demonstrated that CD14 e xpression by macrophages from Crohn's disease and ulcerative colitis w as augmented significantly (P = 0.02 and P = 0.01, respectively) compa red with uninflamed intestine, with a discrete population of macrophag es in inflammatory bowel disease, not present in normal intestine, whi ch strongly expressed CD14. The characteristically high levels of CD14 on blood monocytes were unaffected by the presence of intestinal infl ammation. Given the exposure of lamina propria cells to LPS present in the lumen of the terminal ileum and colon, the increased numbers of C D14(+) macrophages in inflammatory bowel disease may result in greatly increased production of inflammatory mediators, thereby suggesting a mechanism for the perpetuation of mucosal inflammation.