Increased Serum Alkaline Phosphatase Activity Originating from Neutrophilic Leukocytes

Izumi, Masakazu; Ishikawa, Jinko; Takeshita, Akira; Maekawa, Masato

doi:10.1373/clinchem.2005.052621

Cited by 9 publications

(12 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was also related to the formation of fibro-osseous lesion on the femorotibial joint and tartus. This was related with the increase in neutrophil count, as ALP was a component within the neutrophil (13 , 14) . ALP was likewise increased after lenograstim administration (14) , which was attributed to pharmacological activity by G-CSF.…”

Section: Discussionmentioning

confidence: 89%

Four-Week Repeated Intravenous Dose Toxicity and Toxicokinetic Study of TS-DP2, a Novel Human Granulocyte Colony Stimulating Factor in Rats

Lee¹,

Lee²,

Choe³

et al. 2015

Toxicological Research

View full text Add to dashboard Cite

TS-DP2 is a recombinant human granulocyte colony stimulating factor (rhG-CSF) manufactured by TS Corporation. We conducted a four-week study of TS-DP2 (test article) in repeated intravenous doses in male and female Sprague-Dawley (SD) rats. Lenograstim was used as a reference article and was administered intravenously at a dose of 1000 μg/kg/day. Rats received TS-DP2 intravenously at doses of 250, 500, and 1000 μg/kg/day once daily for 4 weeks, and evaluated following a 2-week recovery period. Edema in the hind limbs and loss of mean body weight and body weight gain were observed in both the highest dose group of TS-DP2 and the lenograstim group in male rats. Fibro-osseous lesions were observed in the lenograstim group in both sexes, and at all groups of TS-DP2 in males, and at doses of TS-DP2 500 μg/kg/day and higher in females. The lesion was considered a toxicological change. Therefore, bone is the primary toxicological target of TS-DP2. The lowest observed adverse effect level (LOAEL) in males was 250 μg/kg/day, and no observed adverse effect level (NOAEL) in females was 250 μg/kg/day in this study. In the toxicokinetic study, the serum concentrations of G-CSF were maintained until 8 hr after administration. The systemic exposures (AUC0-24h and C0) were not markedly different between male and female rats, between the administration periods, or between TS-DP2 and lenograstim. In conclusion, TS-DP2 shows toxicological similarity to lenograstim over 4-weeks of repeated doses in rats.

show abstract

Section: Discussionmentioning

confidence: 89%

Four-Week Repeated Intravenous Dose Toxicity and Toxicokinetic Study of TS-DP2, a Novel Human Granulocyte Colony Stimulating Factor in Rats

Lee¹,

Lee²,

Choe³

et al. 2015

Toxicological Research

View full text Add to dashboard Cite

show abstract

“…There is one report of a correlation between human hyperphosphatasemia with an increased B-ALP fraction and the diagnosis of polycythemia vera or chronic granulocytic leukemia. 24 Neither of those diagnoses were considered in the reported case, and generally translation of human cases to veterinary species should be viewed with caution because characteristics of myelomonocytic cells in dogs and people may not be completely identical, including differences at different maturation stages. This is a unique case where hyperphosphatasemia originated, at least partially, from the leukemic population producing a B-ALP isoform, regardless of the exact nature of the leukemia.…”

Section: Discussionmentioning

confidence: 94%

“…To the authors’ knowledge, increased serum B‐ALP activity related to a hematopoietic neoplasia has never been reported in dogs. There is one report of a correlation between human hyperphosphatasemia with an increased B‐ALP fraction and the diagnosis of polycythemia vera or chronic granulocytic leukemia . Neither of those diagnoses were considered in the reported case, and generally translation of human cases to veterinary species should be viewed with caution because characteristics of myelomonocytic cells in dogs and people may not be completely identical, including differences at different maturation stages.…”

Section: Discussionmentioning

confidence: 99%

Marked hyperphosphatasemia associated with an acute leukemia in a Great Dane

Froment

Bédard

2016

Veterinary Clinical Pathol

View full text Add to dashboard Cite

This is the report of a 5-year-old male neutered Great Dane with an extreme leukocytosis (544.9 × 10(9) cells/L; RI 5.2-13.9 × 10(9) cells/L) characterized by highly atypical round cells. Cellular morphologic features such as cytoplasmic membrane blebs, a high nuclear-to-cytoplasmic ratio, and nuclear indentations and irregularities and large nucleoli, as well as immunocytochemistry for CD3 and CD79, myeloperoxidase cytochemistry, and clonality testing were not conclusive for myeloid or lymphoid origin. Marked alkaline hyperphosphatasemia was present at the first visit (2783.0 U/L; RI 6-80.0 U/L), followed by a 5-fold increase (14,000 U/L) a week later, identified as being mostly contributed by the bone-ALP isoform (11,062 U/L; RI 0-30 U/L). In addition, the atypical leukocytes were strongly positive for cytoplasmic ALP activity. In vitro lysis of a heparin blood sample resulted in a 1.7-fold increase of ALP activity, supporting the origin of the hyperphosphatasemia at least in part from the leukemic cell population. To the authors' knowledge, this is a unique case of alkaline hyperphosphatasemia, due at least to a leukemic cell population producing a bone-ALP isoform, regardless of the exact nature of the leukemia.

show abstract

“…These are ALPL (alkaline phosphatase liver/bone/kidney) and MOCS1 (molybdenum cofactor synthesis 1). The ALPL gene is mainly expressed in neutrophils and monocytes [62]. The role of alkaline phosphatase is fundamental as a high number of signal transduction cascades are involved in adaptive processes.…”

Section: Discussionmentioning

confidence: 99%

“…Phosphorylation and dephosphorylation of signal proteins is the key determinant in the phenomenon that regulates the transduction and the amplification of a stimulus from the cell membrane receptor to the nucleus, where the modulation of gene expression occurs. Elevations in plasma alkaline phosphatase, whose sources include neutrophils and monocytes, can be also related to pathological conditions [62]. MOCS1 encodes for a protein involved in the biological activation of molybdenum and it is highly expressed by peripheral white blood cells.…”

Section: Discussionmentioning

confidence: 99%

Breed and adaptive response modulate bovine peripheral blood cells’ transcriptome

Pošćić

Montanari

D’Andrea

et al. 2017

J Animal Sci Biotechnol

View full text Add to dashboard Cite

BackgroundAdaptive response includes a variety of physiological modifications to face changes in external or internal conditions and adapt to a new situation. The acute phase proteins (APPs) are reactants synthesized against environmental stimuli like stress, infection, inflammation.MethodsTo delineate the differences in molecular constituents of adaptive response to the environment we performed the whole-blood transcriptome analysis in Italian Holstein (IH) and Italian Simmental (IS) breeds. For this, 663 IH and IS cows from six commercial farms were clustered according to the blood level of APPs. Ten extreme individuals (five APP+ and APP- variants) from each farm were selected for the RNA-seq using the Illumina sequencing technology. Differentially expressed (DE) genes were analyzed using dynamic impact approach (DIA) and DAVID annotation clustering. Milk production data were statistically elaborated to assess the association of APP+ and APP- gene expression patterns with variations in milk parameters.ResultsThe overall de novo assembly of cDNA sequence data generated 13,665 genes expressed in bovine blood cells. Comparative genomic analysis revealed 1,152 DE genes in the comparison of all APP+ vs. all APP- variants; 531 and 217 DE genes specific for IH and IS comparison respectively. In all comparisons overexpressed genes were more represented than underexpressed ones. DAVID analysis revealed 369 DE genes across breeds, 173 and 73 DE genes in IH and IS comparison respectively. Among the most impacted pathways for both breeds were vitamin B6 metabolism, folate biosynthesis, nitrogen metabolism and linoleic acid metabolism.ConclusionsBoth DIA and DAVID approaches produced a high number of significantly impacted genes and pathways with a narrow connection to adaptive response in cows with high level of blood APPs. A similar variation in gene expression and impacted pathways between APP+ and APP- variants was found between two studied breeds. Such similarity was also confirmed by annotation clustering of the DE genes. However, IH breed showed higher and more differentiated impacts compared to IS breed and such particular features in the IH adaptive response could be explained by its higher metabolic activity. Variations of milk production data were significantly associated with APP+ and APP- gene expression patterns.Electronic supplementary materialThe online version of this article (doi:10.1186/s40104-017-0143-y) contains supplementary material, which is available to authorized users.

show abstract

Increased Serum Alkaline Phosphatase Activity Originating from Neutrophilic Leukocytes

Cited by 9 publications

References 9 publications

Four-Week Repeated Intravenous Dose Toxicity and Toxicokinetic Study of TS-DP2, a Novel Human Granulocyte Colony Stimulating Factor in Rats

Four-Week Repeated Intravenous Dose Toxicity and Toxicokinetic Study of TS-DP2, a Novel Human Granulocyte Colony Stimulating Factor in Rats

Marked hyperphosphatasemia associated with an acute leukemia in a Great Dane

Breed and adaptive response modulate bovine peripheral blood cells’ transcriptome

Contact Info

Product

Resources

About