Nitric oxide and cell viability in inflammatory cells: a role for NO in macrophage function and fate.
Macrophages participate actively in the inflammatory response by releasing cytokines, chemokines and factors that recruit additional cells to sites of infection or tissue injury or alteration. In addition to this, activated macrophages rapidly activate the expression of genes responsible for the high-output synthesis of reactive oxygen and nitrogen species (NO, O2-, H2O2 and peroxynitrite, among others) and bioactive lipids derived from arachidonic acid. All of these agents contribute to the regulation of the inflammatory response. Most of these molecules, when synthesized at these high concentrations, exert pro-apoptotic effects in many cell types. Macrophages themselves are a notable and important exception, being resistant to apoptotic death upon activation. This resistance is necessary to enable these cells to perform their functional role during the early phases of an inflammatory response. However, after cumulative damage, or when the synthesis of inflammatory mediators decreases, macrophages undergo the characteristic mitochondrial-dependent cell death program, contributing in this way to the resolution of the inflammatory reaction. In the case of infectious diseases, this also helps to prevent the development of parasitic strategies by phagocytosed pathogens.
Boscá
Lisardo
L
Centro Nacional de Investigaciones Cardiovasculares, Ronda de Poniente 5, Tres Cantos, 28760 Madrid, Spain. lbosca@cnic.es
Zeini
Miriam
M
Través
Paqui G
PG
Hortelano
Sonsoles
S
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology
D011453:Prostaglandins; D009569:Nitric Oxide