TY - JOUR
T1 - Mutation of mouse Mayp/Pstpip2 causes a macrophage autoinflammatory disease
AU - Grosse, Johannes
AU - Chitu, Violeta
AU - Marquardt, Andreas
AU - Hanke, Petra
AU - Schmittwolf, Carolin
AU - Zeitlmann, Lutz
AU - Schropp, Patricia
AU - Barth, Bettina
AU - Yu, Philipp
AU - Paffenholz, Rainer
AU - Stumm, Gabriele
AU - Nehls, Michael
AU - Stanley, E. Richard
PY - 2006/4/15
Y1 - 2006/4/15
N2 - Macrophage actin-associated tyrosine phosphorylated protein (MAYP)/PSTPIP2, a PCH protein, is involved in the regulation of macrophage motility. Mutations in a closely related gene, PSTPIP1/CD2BP1, cause a dominantly inherited autoinflammatory disorder known as PAPA syndrome. A mutant mouse obtained by chemical mutagenesis exhibited an autoinflammatory disorder characterized by macrophage infiltration and inflammation, leading to osteolysis and necrosis in paws and necrosis of ears. Positional cloning of this recessive mutation, termed Lupo, identified a T to A nucleotide exchange leading to an amino acid substitution (I282N) in the sequence of MAYP. MaypLp/Lp disease was transferable by bone marrow transplantation and developed in the absence of lymphocytes. Consistent with the involvement of macrophages, lesion development could be prevented by the administration of clodronate liposomes. MAYP is expressed in monocytes/macrophages and in a Mac1+ subfraction of granulocytes. LPS stimulation increases its expression in macrophages. Because of the instability of the mutant protein, MAYP expression is reduced 3-fold in MaypLp/Lp macrophages and, on LPS stimulation, does not rise above the level of unstimulated wild-type (WT) cells. MaypLp/Lp mice expressed elevated circulating levels of several cytokines, including MCP-1; their macrophages exhibited altered cytokine production in vitro. These studies suggest that MAYP plays an anti-inflammatory role in macrophages.
AB - Macrophage actin-associated tyrosine phosphorylated protein (MAYP)/PSTPIP2, a PCH protein, is involved in the regulation of macrophage motility. Mutations in a closely related gene, PSTPIP1/CD2BP1, cause a dominantly inherited autoinflammatory disorder known as PAPA syndrome. A mutant mouse obtained by chemical mutagenesis exhibited an autoinflammatory disorder characterized by macrophage infiltration and inflammation, leading to osteolysis and necrosis in paws and necrosis of ears. Positional cloning of this recessive mutation, termed Lupo, identified a T to A nucleotide exchange leading to an amino acid substitution (I282N) in the sequence of MAYP. MaypLp/Lp disease was transferable by bone marrow transplantation and developed in the absence of lymphocytes. Consistent with the involvement of macrophages, lesion development could be prevented by the administration of clodronate liposomes. MAYP is expressed in monocytes/macrophages and in a Mac1+ subfraction of granulocytes. LPS stimulation increases its expression in macrophages. Because of the instability of the mutant protein, MAYP expression is reduced 3-fold in MaypLp/Lp macrophages and, on LPS stimulation, does not rise above the level of unstimulated wild-type (WT) cells. MaypLp/Lp mice expressed elevated circulating levels of several cytokines, including MCP-1; their macrophages exhibited altered cytokine production in vitro. These studies suggest that MAYP plays an anti-inflammatory role in macrophages.
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U2 - 10.1182/blood-2005-09-3556
DO - 10.1182/blood-2005-09-3556
M3 - Article
C2 - 16397132
AN - SCOPUS:33645734214
SN - 0006-4971
VL - 107
SP - 3350
EP - 3358
JO - Blood
JF - Blood
IS - 8
ER -