C2-ceramide primes specifically for the superoxide anion production induced by N-formylmethionylleucyl phenylalanine (fMLP) in human neutrophils

Ceramide 1-Phosphate Formation in Neutrophils

“…In neutrophils or granulocytes differentiated from HL60 cells, Cer has been shown to regulate intracellular signaling pathways, including p21-activated protein kinases [5], mitogen-activated protein kinase [9]and phospholipase D [3]. Accordingly, intracellular Cer levels must be strictly controlled, and it is possible to postulate that phosphorylation of Cer inactivates it as a signaling molecule in the same way in which the phosphorylation of diacylglycerol stops the activation of protein kinase C. In this context, it is worth noting that Cer, but not Cer-1-P, primes for the superoxide anion production induced by fMLP in human neutrophils [7]and that Cer inhibits IgG-dependent phagocytosis [8], while Cer-1-P may promote phagolysosome formation, a critical event in phagocytosis [4]. …”

“…This lysophospholipid mediator is attracting great attention as a unique mediator acting both as an intracellular second messenger and an extracellular ligand (interacting with Endothelial Differentiation Gene). Neutrophils, which play a crucial role in host defense by phagocytosis and elimination of invading microorganisms, are no exception in that sphingolipid mediators are involved in the regulation of their functional responses (see Discussion) [3, 4, 5, 6, 7, 8, 9]. …”

A cell-autonomous requirement for neutral sphingomyelinase 2 in bone mineralization

“…Smpd3 encodes neutral sphingomyelinase 2 (nSMase2), a membrane-bound enzyme, which cleaves sphingomyelin to generate the lipid second messenger ceramide. Ceramide generated by sphingomyelinases or by a de novo pathway affects a wide range of cellular processes, including cell death, proliferation, and differentiation (Obeid et al, 1993;Bose et al, 1995;Richard et al, 1996;Sanchez-Alavez et al, 2006).…”

A cell-autonomous requirement for neutral sphingomyelinase 2 in bone mineralization

“…Smpd3 encodes neutral sphingomyelinase 2 (nSMase2), a membrane-bound enzyme, which cleaves sphingomyelin to generate the lipid second messenger ceramide. Ceramide generated by sphingomyelinases or by a de novo pathway affects a wide range of cellular processes, including cell death, proliferation, and differentiation (Obeid et al, 1993;Bose et al, 1995;Richard et al, 1996;SanchezAlavez et al, 2006).…”