Molecular mechanisms involved in the inhibition of neutrophil locomotion by tumor cells.

A chronic myelogenous leukemia cell line (K562) releases a factor of about 8 kD which we have named K562-inhibitory factor (K562-IF) because it inhibits neutrophil locomotion. This factor has potent anti-inflammatory activity in mice, associated with an inhibition of neutrophil function including not only random locomotion and fMetLeuPhe- or serum-induced locomotion but also adherence and zymosan-induced chemiluminescence and degranulation. In contrast, K562-IF does not affect the oxidative burst induced by soluble compounds such as fMetLeuPhe and phorbol esters. Analysis of the mechanism of action of K562-IF on neutrophils showed that it involves an adherence protein, mainly CR3 (the receptor of complement fraction iC3b). Neither, CR3 expression nor its up-regulation were altered, whereas the function of CR3 was depressed, i.e., it failed to cap upon neutrophil stimulation and did not bind iC3b. One unexplained finding is that K562-IF inhibits actin polymerization induced by fMetLeuPhe but not by activation of the Fc-gamma receptor III. Studies are underway to establish whether K562 cells are representative of other malignant cells with regard to the production of neutrophil inhibitors.