Neutrophil granulocytes uniquely express, among human blood cells, high levels of Methionine-sulfoxide-reductase enzymes.
L-Methionine (Met), in its free form or when inserted in proteins, is sensitive to oxidation of its thioether group by reactive oxygen species from exogenous or endogenous sources. Two stable diastereomers of Met sulfoxide [Met-(O)] may be formed [Met-S-(O) and Met-R-(O)], but these can be reduced by two classes of Methionine-sulfoxide-reductase (Msr) enzymes: MsrA, which reduces the S, and MsrB, which reduces the R sulfoxide. In this study, we have examined the levels of expression of Msr in human blood cells by enzymatic activity assay, Western blotting, and RT-PCR of purified populations of polymorphonuclear neutrophils and eosinophils, mononuclear cells, platelets, and erythrocytes. Our data indicate that of the blood cells analyzed, neutrophils expressed the highest activity, which was mainly of MsrB type. During degranulation of activated neutrophils, Msr activity was not released but remained confined within the cell, indicating a non-granular localization. Immunoprecipitation and RT-PCR studies indicated the almost complete lack of mitochondrial forms of Msrs in granulocytes. It is thus likely that Msrs are important as antioxidant/repair systems for neutrophils, cells with enormous capacity for the generation of reactive oxidants and hence, susceptible to oxidative damage.
Achilli
Cesare
C
Department of Biochemistry, University of Pavia, via Bassi 21, 27100 Pavia, Italy.
Ciana
Annarita
A
Rossi
Antonio
A
Balduini
Cesare
C
Minetti
Giampaolo
G
D002478:Cells, Cultured; D004789:Enzyme Activation; D020869:Gene Expression Profiling; D006098:Granulocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*; D006801:Humans; D047468:Immunoprecipitation; D007963:Leukocytes, Mononuclear / Q000201:enzymology* / Q000276:immunology*; D051150:Methionine Sulfoxide Reductases; D010088:Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000235:genetics / Q000276:immunology
D010088:Oxidoreductases; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase