Disease relevance of Acp5

• Anti-c-Fms mAb selectively and completely arrested the profound pathological osteoclastogenesis attending this condition, the significance of which is reflected by similar blunting of the in vivo bone resorption marker tartrate-resistant acid phosphatase 5b (TRACP 5b) [1].
• Mice lacking tartrate-resistant acid phosphatase (Acp 5) have disrupted endochondral ossification and mild osteopetrosis [2].
• Mice lacking tartrate-resistant acid phosphatase (Acp 5) have disordered macrophage inflammatory responses and reduced clearance of the pathogen, Staphylococcus aureus [3].
• Specifically, TRACP(-/-) mice had defective delayed hypersensitivity responses to picryl chloride and reduced proliferative responses to ovalbumin compared with wildtype mice [4].

High impact information on Acp5

• Tartrate-resistant acid phosphatase (TRACP; a marker enzyme of osteoclasts)-positive cells appeared only when bone marrow cells were cultured in contact with OP6L7 cells and both rhM-CSF and 1 alpha, 25 (OH)2D3 were added [5].
• Microscopic analyses showed an accumulation of osteopontin adjacent to actively resorbing osteoclasts of Acp5- and LAP/Acp5-deficient mice [6].
• Overlapping functions of lysosomal acid phosphatase (LAP) and tartrate-resistant acid phosphatase (Acp5) revealed by doubly deficient mice [6].
• This is further supported by biochemical analyses that demonstrate strongly reduced dephosphorylation of osteopontin incubated with LAP/Acp5-deficient bone extracts [6].
• To date, two lysosomal acid phosphatases are known to be expressed in cells of the monocyte/phagocyte lineage: the ubiquitously expressed lysosomal acid phosphatase (LAP) and the tartrate-resistant acid phosphatase-type 5 (Acp5) [6].

Biological context of Acp5

• The binding sites for both of these factors have been identified, and they have been determined to be functional in regulating TRACP expression [7].
• Increased mineralization density was observed in the long bones of older animals which showed modelling deformities at their extremities: heterozygotes and homozygous Acp 5 mutant mice had tissue that was more mineralized and occupied a greater proportion of the bone in all regions [2].
• Animals homozygous for the null Acp 5 allele had progressive foreshortening and deformity of the long bones and axial skeleton but apparently normal tooth eruption and skull plate development, indicating a rôle for Acp 5 in endochondral ossification [2].
• Osteoclast differentiation was determined by TRACP staining, and cell cycle regulation was determined by BrdU uptake and flow cytometric analysis [8].
• Previous studies suggest that ROS generated by TRACP may participate in degradation of endocytosed bone matrix products in resorbing osteoclasts and degradation of foreign compounds during antigen presentation in activated macrophages [9].

Anatomical context of Acp5

• Macrophages from TRACP+ mice showed increased capacity of bacterial killing [9].
• Osteoclastic tartrate-resistant acid phosphatase (Acp 5): its localization to dendritic cells and diverse murine tissues [10].
• In alveolar macrophages, TRACP is colocalized with endocytosed Staphylococcus aureus, a pathogen whose clearance is reduced in TRACP-deficient mice, suggesting that ROS generated by TRACP may be targeted to destroy foreign material in the antigen presentation route of macrophages [11].
• We postulate that TRACP has an important role in the presentation of antigens to T cells [4].
• TRACP, a marker of osteoclasts, is also expressed by cells of the immune system [4].

Associations of Acp5 with chemical compounds

• Nitric oxide production was increased in activated macrophages of WT mice, but not in TRACP+ mice [9].
• Superoxide formation and nitrite production were enhanced in stimulated macrophages lacking TRACP as was the secretion of the proinflammatory cytokines TNF-alpha, interleukin (IL)-1beta, and IL-12 [12].
• Dexamethasone greatly potentiated TRACP-positive MNC formation induced by 1 alpha,25-(OH)2D3, whereas the glucocorticoid alone had no effect on it [13].
• Isobutylmethylxanthine potentiated the production of TRACP-positive cells induced by CCP [14].
• Furthermore, the calcium ionophore A23187 significantly increased the formation of TRACP-positive MNCs [15].

Regulatory relationships of Acp5

• Salmon calcitonin enhanced cAMP production in the cocultures only when TRACP-positive cells were formed [13].
• In organ cultures of neonatal mouse calvaria, activin also enhanced the generation of TRACP-positive giant cells in the endosteal periosteum and increased the TRACP staining of whole calvaria, but did not exhibit bone resorbing activity [16].
• Monospecific anti-mouse recombinant IL-1 alpha serum inhibited TRACP-positive multinucleated cell formation in the presence of paraformaldehyde-fixed P388D1 cells stimulated with LPS [17].

Other interactions of Acp5

• We have shown that TRACP expression is a target for regulation by the macrophage/osteoclast transcription factor PU.1 and the osteoclast commitment factor MiTF and that these factors act synergistically in regulating this promoter [7].
• In contrast, p21/p27 double knockout mice developed osteopetrosis, with fewer osteoclasts that exhibited lower TRACP activity and abnormal cell morphology present in long bone [18].
• Reserpine also modestly enhanced the expression of the osteoclast marker TRACP in the absence of RANKL [19].
• To examine whether RANK overexpression induced osteoclastogenesis, osteoclast progenitors that were derived from wildtype bone marrow cells, in which RANK was overexpressed, were cultured with monocyte-macrophage colony-stimulating factor (M-CSF), and TRACP staining was performed [20].
• Osteoclasts were defined as tartrate-resistant acid phosphatase-positive multinucleated cells (TRACP-positive MNCs) in which specific calcitonin receptors were identified by autoradiography with labeled salmon calcitonin [21].

Analytical, diagnostic and therapeutic context of Acp5

• In contrast, osteoblastic MC3T3-E1 cells failed to induce TRACP-positive cells in the cocultures [13].
• Mouse marrow cells cultured for 8 days with 10 nM 1 alpha, 25(OH)2D3 and freshly isolated authentic mouse osteoclasts were incubated with [125I]-salmon CT in the presence or absence of excess amounts of unlabeled CT, stained for TRACP, and processed for autoradiography [22].
• One antibody, 220, was tested for its epitope specificity and use in various immunological techniques. rTRACP 5a had properties identical to serum TRACP 5a [23].
• Antibody 220 was effective for specific immunoprecipitation, immunoassay, and immunoblot of TRACP 5a [23].
• In cytocentrifuge preparations and frozen sections of mouse spleen, TR-AP was demonstrated after simultaneous incubation with substrate and tartrate [24].

References