Myeloid cell function in MRP-14 (S100A9) null mice
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Myeloid cell function in MRP-14 (S100A9) null mice. / Hobbs, Josie A R; May, Richard; Tanousis, Kiki; McNeill, Eileen; Mathies, Margaret; Gebhardt, Christoffer; Henderson, Robert; Robinson, Matthew J; Hogg, Nancy.
In: MOL CELL BIOL, Vol. 23, No. 7, 04.2003, p. 2564-76.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Myeloid cell function in MRP-14 (S100A9) null mice
AU - Hobbs, Josie A R
AU - May, Richard
AU - Tanousis, Kiki
AU - McNeill, Eileen
AU - Mathies, Margaret
AU - Gebhardt, Christoffer
AU - Henderson, Robert
AU - Robinson, Matthew J
AU - Hogg, Nancy
PY - 2003/4
Y1 - 2003/4
N2 - Myeloid-related protein 14 (MRP-14) and its heterodimeric partner, MRP-8, are cytosolic calcium-binding proteins, highly expressed in neutrophils and monocytes. To understand the function of MRP-14, we performed targeted disruption of the MRP-14 gene in mice. MRP-14(-/-) mice showed no obvious phenotype and were fertile. MRP-8 mRNA but not protein is present in the myeloid cells of these mice, suggesting that the stability of MRP-8 protein is dependent on MRP-14 expression. A compensatory increase in other proteins was not detected in cells lacking MRP-8 and MRP-14. Although the morphology of MRP-14(-/-) myeloid cells was not altered, they were significantly less dense. When Ca(2+) responses were investigated, there was no change in the maximal response to the chemokine MIP-2. At lower concentrations, however, there was reduced responsiveness in MRP-14(-/-) compared with MRP-14(+/+) neutrophils. This alteration in the ability to flux Ca(2+) did not impair the ability of the MRP-14(-/-) neutrophils to respond chemotactically to MIP-2. In addition, the myeloid cell functions of phagocytosis, superoxide burst, and apoptosis were unaffected in MRP-14(-/-) cells. In an in vivo model of peritonitis, MRP-14(-/-) mice showed no difference from wild-type mice in induced inflammatory response. The data indicate that MRP-14 and MRP-8 are dispensable for many myeloid cell functions.
AB - Myeloid-related protein 14 (MRP-14) and its heterodimeric partner, MRP-8, are cytosolic calcium-binding proteins, highly expressed in neutrophils and monocytes. To understand the function of MRP-14, we performed targeted disruption of the MRP-14 gene in mice. MRP-14(-/-) mice showed no obvious phenotype and were fertile. MRP-8 mRNA but not protein is present in the myeloid cells of these mice, suggesting that the stability of MRP-8 protein is dependent on MRP-14 expression. A compensatory increase in other proteins was not detected in cells lacking MRP-8 and MRP-14. Although the morphology of MRP-14(-/-) myeloid cells was not altered, they were significantly less dense. When Ca(2+) responses were investigated, there was no change in the maximal response to the chemokine MIP-2. At lower concentrations, however, there was reduced responsiveness in MRP-14(-/-) compared with MRP-14(+/+) neutrophils. This alteration in the ability to flux Ca(2+) did not impair the ability of the MRP-14(-/-) neutrophils to respond chemotactically to MIP-2. In addition, the myeloid cell functions of phagocytosis, superoxide burst, and apoptosis were unaffected in MRP-14(-/-) cells. In an in vivo model of peritonitis, MRP-14(-/-) mice showed no difference from wild-type mice in induced inflammatory response. The data indicate that MRP-14 and MRP-8 are dispensable for many myeloid cell functions.
KW - Animals
KW - Calcium
KW - Calgranulin A
KW - Calgranulin B
KW - Cell Count
KW - Cells, Cultured
KW - Chemokine CXCL2
KW - Chemokines
KW - Dose-Response Relationship, Drug
KW - Fluorescent Dyes
KW - Gene Expression Regulation, Developmental
KW - Gene Targeting
KW - Mice
KW - Mice, Knockout
KW - Monocytes
KW - Myeloid Cells
KW - Neutrophils
KW - Peritonitis
KW - Phenotype
KW - RNA, Messenger
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
M3 - SCORING: Journal article
C2 - 12640137
VL - 23
SP - 2564
EP - 2576
JO - MOL CELL BIOL
JF - MOL CELL BIOL
SN - 0270-7306
IS - 7
ER -