Description
FS-C3H cells are a unique and extensively studied cancer cell line derived from the C3H/HeJ mouse, a strain known for its resistance to endotoxin. These cells have been instrumental in unravelling the complex mechanisms underlying host responses to endotoxin, serving as a valuable comparative model. Researchers have primarily focused on this strains B lymphocytes and macrophages, which exhibit a remarkable inability to be activated by LPS (lipopolysaccharide), a key component of bacterial endotoxin. One intriguing aspect of FS-C3H cells is the absence or alteration of a receptor that transduces an activation signal, leading to their nonresponsiveness to LPS. While specific LPS binding proteins have been identified in lymphocytes and other cells, the elusive receptor responsible for mediating the activation signal in responder cells has yet to be isolated. This knowledge gap has driven investigations into the signal transduction pathways employed by FS-C3H B cells when stimulated by a protein mitogen, revealing striking similarities to those used by LPS responder cells. Notably, protein kinase C (PKC) and tyrosine kinase, two enzymes responsible for phosphorylating signal proteins within cells, are operational in FS-C3H B cells, akin to their LPS-responsive counterparts. DNA synthesis is inhibited in both cases upon blocking either PKC or tyrosine kinase activity. However, it is worth highlighting that inhibiting tyrosine kinase activity also hampers PKC-stimulated DNA synthesis, indicating a regulatory role for tyrosine kinase-initiated phosphorylation in the PKC signalling pathway. Further analysis of the phosphorylated proteins in both LPS responder and FS-C3H B cells are warranted to gain a deeper understanding of the underlying molecular events. This will illuminate whether the defect in FS-C3H cells lies within the signal pathway leading to gene activation and proliferation. Despite ongoing investigations, the hypothesis of a missing or defective signal receptor remains a plausible explanation for the hyporesponsiveness of FS-C3H cells to LPS. Hence, isolating the Lpsn gene and its product holds promise in providing the necessary evidence for a more unmistakable comprehension of the interactions between LPS and cells. FS-C3H cells offer a valuable research tool for scientists aiming to comprehend the intricate genetic control mechanisms governing host responses to endotoxin. By utilizing this comparative model, researchers can delve into the signal transduction pathways, phosphorylation events, and potential receptor abnormalities, paving the way for significant advancements in understanding LPS-cell interactions and associated cellular processes