Hobbs Josie A R, May Richard, Tanousis Kiki, McNeill Eileen, Mathies Margaret, Gebhardt Christoffer, Henderson Robert, Robinson Matthew J, Hogg Nancy
Leukocyte Adhesion Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, London WC2A 3PX, United Kingdom.
Mol Cell Biol. 2003 Apr;23(7):2564-76. doi: 10.1128/MCB.23.7.2564-2576.2003.
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.
髓系相关蛋白14（MRP - 14）及其异源二聚体伴侣MRP - 8是胞质钙结合蛋白，在中性粒细胞和单核细胞中高度表达。为了解MRP - 14的功能，我们对小鼠的MRP - 14基因进行了靶向破坏。MRP - 14基因敲除（MRP - 14(-/-)）小鼠未表现出明显的表型，且可育。在这些小鼠的髓系细胞中存在MRP - 8 mRNA但不存在蛋白质，这表明MRP - 8蛋白的稳定性依赖于MRP - 14的表达。在缺乏MRP - 8和MRP - 14的细胞中未检测到其他蛋白的代偿性增加。尽管MRP - 14(-/-)髓系细胞的形态未改变，但它们的密度显著降低。当研究钙离子（Ca(2+)）反应时，对趋化因子MIP - 2的最大反应没有变化。然而，在较低浓度下，与MRP - 14基因野生型（MRP - 14(+/+)）中性粒细胞相比，MRP - 14(-/-)中性粒细胞的反应性降低。这种钙离子通量能力的改变并未损害MRP - 14(-/-)中性粒细胞对MIP - 2进行趋化反应的能力。此外，MRP - 14(-/-)细胞的吞噬作用、超氧化物爆发和凋亡等髓系细胞功能未受影响。在腹膜炎的体内模型中，MRP - 14(-/-)小鼠在诱导的炎症反应方面与野生型小鼠没有差异。数据表明，MRP - 14和MRP - 8对于许多髓系细胞功能是可有可无的。
