Functional abnormalities in protein tyrosine phosphatase epsilon-deficient macrophages.
Protein tyrosine phosphatase epsilon (PTP epsilon)-deficient mice were generated by targeted deletion of exons 3, 4, and 5 of the Ptpre gene. Mice homozygous for this deletion (Ptpre(Delta3-5)) were fertile, bred and developed normally and exhibited no overt phenotype. However, closer examination of the function of macrophages from these mice revealed a defect in the regulation of the respiratory burst. While bacterial lipopolysaccharide (LPS) or tumour necrosis factor alpha (TNFalpha) were able to prime bone marrow-derived macrophages (BMM) from wild type (Ptpre(+)) macrophages for an enhanced respiratory burst, they were unable to do so in macrophages from PTP epsilon-deficient mice. PTP epsilon-deficient BMM also had abnormalities in cytokine production with a reduced ability to produce TNFalpha and enhanced IL-10 production in response to challenge with LPS. These findings suggest an important role for PTP epsilon in the control of macrophage function.
Sully
V
V
Trescowthick Research Laboratories, Peter MacCallum Cancer Institute, A'Beckett Street, Melbourne, Victoria 8006, Australia.
Pownall
S
S
Vincan
E
E
Bassal
S
S
Borowski
A H
AH
Hart
P H
PH
Rockman
S P
SP
Phillips
W A
WA
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D006720:Homozygote; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D051379:Mice; D010641:Phenotype; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000494:pharmacology
D017931:DNA Primers; D007527:Isoenzymes; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D017027:Protein Tyrosine Phosphatases