Human Peripheral Blood Granulocytes

A central problem of the current studies on protooncogenes (cellular oncogenes, c-onc) is their role in the control of growth and differentiation of normal cells. The cfos protooncogene has been widely investigated and it has been demonstrated that cfos specific transcripts are induced in proliferating cells (1, 2) and during differentiation (3-6) . In particular, when HL60 (promyelocytic) and U937 (promonocytic cell line) are induced to differentiate to cells with the characteristics of monocytes/macrophages by treatment with PMA or IFN-1' (46), cfos mRNA is detectable within 10 min . Similarly, when the murine myelomonocytic leukemia WEHI-3B was induced to differentiate to monocytes by granulocyte colony-stimulating factor (GCSF) and Actinomycin D, expression of cfos was seen (4). Along the same line, when human myeloid leukemias at different stages of differentiation were examined, cfos transcripts were only detectable in the more mature monocytic forms (7) . Moreover, freshly isolated murine peritoneal macrophages express appreciable levels of cfos-specific mRNA, which can be augmented by endotoxin (8) and colony-stimulating factor 1 (CSF-1) (4). Thus, although expression of cfos may be neither sufficient nor obligatory for the differentiation of mononuclear phagocytes (6), and it has been suggested (6) that cfos expression plays a role only in growth arrest of immature myeloid elements, its consistent association with mononuclear phagocytes suggests that this protooncogene may be important in this hematopoietic pathway. Since HL60 cells induced to differentiate to granulocytes do not express appreciable levels ofcfos transcripts (5), expression of this protooncogene in leukocytes in the absence of proliferation appears restricted to monocytes/macrophages . We have examined the presence of cfos-specific transcripts in freshly isolated human leukocyte populations . Unexpectedly, polymorphonuclear leukocytes (PMN) constitutively expressed high levels of cfos mRNA . Monocytes expressed appreciable cfos transcripts, though at much lower levels than PMN, and lymphoid cells showed no detectable expression . Exposure of PMN to agents that stimulate their function resulted in augmented levels of cfos transcripts . Thus, expression of this protooncogene is not peculiar, among circulating leukocytes,