Differing signal requirements for the activation of macrophages from C3H/HeJ and C3H/OuJ mice

Abstract

Endotoxin-associated protein (EP) from Salmonella typhi stimulated the release of prostaglandin E2 (PGE2), interleukin-1 (IL-1), and interferon (IFN) activity in macrophages from the lipopolysaccharide (LPS) responder C3H/OuJ mouse strain. However, only PGE2 and IL-1 were stimulated by EP in macrophages from the LPS nonresponder C3H/HeJ mouse strain. LPS stimulated the release of PGE2, IL-1 and IFN activity in C3H/OuJ macrophages, but not in C3H/HeJ macrophages. The protein kinase C (PKC) activator phorbol myristic acid (PMA) stimulated PGE2 production in both strains but not IL-1 production, suggesting that signalling pathways other than PKC may be involved in IL-1 production. The calcium ionophore ionomycin stimulated PGE2 production in C3H/OuJ but not C3H/HeJ macrophages, suggesting a defective calcium-related pathway in the C3H/HeJ macrophages as compared to the C3H/OuJ cells.

Lipopolysaccharide-induced vacuoles in macrophages: Their origin is plasma membrane-derived organelles and endoplasmic reticulum, but not lysosomes

“…3 They express internalized and digested materials on the cell surface in the context of major histocompatibility antigens for the interaction with lymphocytes. 4 Furthermore, these cells can secrete various proteinaceous cytokines, such as interleukins (IL-1, IL-6, IL-8, IL-10, IL-12), tumor necrosis factor-α (TNF-α), interferon-α, -β (IFN-α, IFN-β) and colony stimulating factors (G-CSF, M-CSF, GM-CSF) 5 and non-proteinaceous reactive substances, such as arachidonate cascade products, 6,7 nitric oxide 4,[8][9][10] and reactive oxygen intermediates. 11,12 Lipopolysaccharide (LPS) is a component of outer membranes of Gram-negative bacteria, and is a strong activator of macrophages.…”