Adhesion of tumoricidal eosinophils to MCA-38 colon adenocarcinoma cells involves protein tyrosine kinase activation and is diminished by elevated cyclic AMP in the effector cell

Although eosinophils have been implicated in immune responses to certain ty pes of tumors, the mechanisms of anti-tumor activity by eosinophils are poo rly understood. We show here that mouse eosinophils kill allogeneic MCA-38 colon adenocarcinoma cells in the absence of specific antibody. Eosinophil adhesion to MCA-38 monolayers occurred within 15 min and plateaued at 90 mi n. Although mouse eosinophils express alpha(L) (CD11a), alpha(M) (CD11b), a nd alpha(4) (CD49d) integrin chains, blocking antibody studies revealed tha t these molecules are not involved in eosinophil binding to MCA-38 cells. A dhesion was also fibronectin-independent. Binding was inhibited when eosino phils, but not MCA-38 cells, were pretreated with methyl 2,5-dihydroxycinna mate (MDHC), a selective inhibitor of protein tyrosine kinases, or 8-Br-cAM P-Na, a cell-permeable cyclic AMP analogue. Adhesion was unaffected by calp hostin C, a specific inhibitor of protein kinase C, and wortmannin, a selec tive inhibitor of phosphatidylinositol 3-kinases.