In vitro cell aggregation and cell adhesion molecules in Crohn's disease

Background: Lack of a suitable model has hindered efforts to understand inflammation and granuloma formation in Crohn's disease. Methods: Granulomalike aggregates of circulating mononuclear cells are produced in vitro by cultures of cells with polyacrylamide beads. To identify features of in vitro aggregates, which are similar to tissue granulomas of Crohn's disease, the gross morphology and immunohistological appearance of the aggregates produced with peripheral blood mononuclear cells from patients with Crohn's disease were analyzed, and the size of in vitro aggregates was correlated with clinical activity of the disease. Blocking antibodies were used to evaluate the role of cell-adhesion molecules in the formation of in vitro aggregates. Results: The size of in vitro aggregates correlates very significantly with clinical activity (P < 0.001). In active Crohn's disease, in vitro aggregates show immunohistological features of hypersensitivity type granulomas. Blocking antibodies against leukocyte function associated antigen LFA-2 (CD2), LFA-3 (CD58), and Mac-1 (CD11b/CD18) inhibit in vitro aggregate formation. Conclusion: In vitro aggregates model in vivo granulomas in size and organization. Cell adhesion molecules like CD2, CD58, and CD 11b/CD18 may be involved in granuloma-formation of Crohn's disease.