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PubMed · 12640137

Myeloid cell function in MRP-14 (S100A9) null mice.

Josie A R Hobbs·Richard May·Kiki Tanousis·Eileen McNeill·Margaret Mathies·Christoffer Gebhardt·Robert Henderson·Matthew J Robinson·Nancy Hogg
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Abstract

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.

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AnimalsCalciumCalgranulin ACalgranulin BCell CountCells, CulturedChemokine CXCL2ChemokinesDose-Response Relationship, DrugFluorescent DyesGene Expression Regulation, DevelopmentalGene TargetingMiceMice, KnockoutMonocytesMyeloid CellsNeutrophilsPeritonitisPhenotypeRNA, MessengerJournal ArticleResearch Support, Non-U.S. Gov't

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Josie A R Hobbs, Richard May, Kiki Tanousis, Eileen McNeill, Margaret Mathies, Christoffer Gebhardt, Robert Henderson, Matthew J Robinson, Nancy Hogg. 2003. Myeloid cell function in MRP-14 (S100A9) null mice.. https://doi.org/10.1128/mcb.23.7.2564-2576.2003

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