Functional abnormalities in protein tyrosine phosphatase epsilon-deficientmacrophages

Protein tyrosine phosphatase epsilon (PTP epsilon)-deficient mice were gene rated by targeted deletion of exons 3, 4, and 5 of the Ptpre gene. Mice hom ozygous for this deletion (Ptpre(Delta3.5)) were fertile, bred and develope d normally and exhibited no overt phenotype. However, closer examination of the function of macrophages from these mice revealed a defect in the regul ation of the respiratory burst. While bacterial lipopolysaccharide (LPS) or tumour necrosis factor alpha (TNF alpha) were able to prime bone marrow-de rived macrophages (BMM) from wild type (Ptpre(+)) macrophages for an enhanc ed respiratory burst, they were unable to do so in macrophages from PTP eps ilon -deficient mice. PTP epsilon -deficient BMM also had abnormalities in cytokine production with a reduced ability to produce TNFa 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. (C) 2 001 Academic Press.