Neutrophil transepithelial migration: regulation at the apical epithelial surface by Fc-mediated events

Neutrophil (PMN) transepithelial migration is a major effector of epithelia l defense in inflammatory diseases involving mucosal surfaces. However, maj or receptor-ligand interactions between epithelial cells and PMN remain inc ompletely characterized. To better define the molecular events involved in PMN interactions with epithelial cells, we produced a monoclonal antibody c alled g82 that inhibited PMN transepithelial migration in the physiological basolateral-to-apical direction. The g82 antigen localized to the apical s urface of human colonic epithelium and was significantly upregulated under inflammatory conditions. Immunoprecipitation revealed two polypeptides of M -r 207 and 32 kDa. F(ab')(2) fragments from g82 IgG had no effect on transm igration, suggesting Fc dependence. Further experiments confirmed dependenc e on the PMN Fc receptor CD32A and that the observed effects were secondary to a failure of PMN to detach from the apical epithelial surface. These Fc -mediated events were epitope specific since binding, isotype-matched antib odies did not affect detachment. These results identify a new mechanism for retention of PMN at the apical epithelial surface following transepithelia l migration. This pathway may be important in pathogen clearance and mucosa l pathophysiology associated with autoimmunity.