Establishment of murine macrophage hybridoma clones capable of acquiring tumoricidal activity upon activation with recombinant interferon-gamma and lipopolysaccharide.

Murine macrophage hybridoma clones were established by fusing glycogen-elicited peritoneal exudate cells (glycogen-PEC) derived from C3H/HeN mice and the hypoxanthine-aminopterin-thymidine-sensitive murine macrophage cell line, J774.3-2. The macrophage hybridomas were further screened for the capacity to acquire tumoricidal activity upon stimulation with lipopolysaccharide (LPS) and recombinant interferon-gamma (IFN-gamma) using murine mammary adenocarcinoma MM48 cells as targets, and three macrophage hybridoma clones, KM-1, KM-2, and KM-3, were established. With concomitant stimulation with LPS, IFN-gamma activated these hybridomas dose dependently to exhibit high tumoricidal activity, whereas single stimulation with either INF-gamma or LPS, even with higher concentrations, did not activate the macrophage hybridomas. This contrasted with the activation of glycogen-PEC for eliciting tumoricidal activity with a single stimulation with LPS (greater than 1 ng/ml) or IFN-gamma (greater than 10 IU/ml). Thus, the macrophage hybridoma clones established here represent inflammatory macrophages which require both IFN-gamma and LPS for their activation.