Novel insights into the biological function of mast cell carboxypeptidase A

Pejler, Gunnar; Knight, Stefan D.; Henningsson, Frida; Wernersson, Sara

doi:10.1016/j.it.2009.04.008

Cited by 69 publications

(75 citation statements)

References 76 publications

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“…4A). At these conditions, we also observed solubilization of CPA3, CPA3 being a mast cell-specific granule protease (19) (Fig. 4B), as well as solubilization of enzymatic activity toward Z-Phe-Arg-AMC, a substrate commonly used for detection of lysosomal cysteine cathepsin activity (Fig.…”

Section: Active Caspase-3 Is Found Within Granule-like Compartments Imentioning

confidence: 61%

Active Caspase-3 Is Stored within Secretory Compartments of Viable Mast Cells

Garcia-Faroldi

Melo

Rönnberg

et al. 2013

The Journal of Immunology

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Caspase-3 is a main executioner of apoptotic cell death. The general notion is that, in viable cells, caspase-3 is found as a cytosolic inactive proenzyme and that caspase-3 activation is largely confined to processes associated with cell death. In this study, we challenge this notion by showing that enzymatically active caspase-3 is stored in viable mast cells. The enzymatically active caspase-3 was undetectable in the cytosol of viable cells, but was recovered in subcellular fractions containing secretory granule-localized proteases. Moreover, active caspase-3 was rapidly released into the cytosolic compartment after permeabilization of the secretory granules. Using a cell-permeable substrate for caspase-3, the presence of active caspase-3–like activity in granule-like compartments close to the plasma membrane was demonstrated. Moreover, it was shown that mast cell activation caused release of the caspase-3 to the cell exterior. During the course of mast cell differentiation from bone marrow cells, procaspase-3 was present in cells of all stages of maturation. In contrast, active caspase-3 was undetectable in bone marrow precursor cells, but increased progressively during the process of mast cell maturation, its accumulation coinciding with that of a mast cell–specific secretory granule marker, mouse mast cell protease 6. Together, the current study suggests that active caspase-3 can be stored within secretory compartments of viable mast cells.

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Section: Active Caspase-3 Is Found Within Granule-like Compartments Imentioning

confidence: 61%

Active Caspase-3 Is Stored within Secretory Compartments of Viable Mast Cells

Garcia-Faroldi

Melo

Rönnberg

et al. 2013

The Journal of Immunology

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“…Specifically, histamine causes vasodilation, increases vascular permeability and, together with leukotrienes and prostaglandins, favors the recruitment of defense cells, such as neutrophils, eosinophils and macrophages 28,29 .…”

Section: Discussionmentioning

confidence: 99%

Effect of laser therapy on the inflammatory response induced by endodontic medications implanted into the subcutaneous tissue of rats

Matos

Soares

Júnior

et al. 2014

Rev. odontol. UNESP

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ResumoIntrodução: Medicamentos endodônticos apresentam componentes tóxicos que provocam algum grau de reação inflamatória. Objetivo: Este estudo avaliou o efeito da laserterapia na resposta inflamatória causada por medicações intracanais, em tecido subcutâneo de ratos, por meio da análise quantitativa de mastócitos. Material e método: Tubos de polietileno contendo as medicações foram implantados no dorso de 60 ratos, distribuídos em seis grupos: HS (pasta de hidróxido de cálcio P.A.); HL (pasta de hidróxido de cálcio P.A. e laserterapia); HPS (pasta de hidróxido de cálcio P.A. com paramonoclorofenol canforado); HPL (pasta de hidróxido de cálcio P.A. com paramonoclorofenol canforado e laserterapia); IS (iodofórmio e soro fisiológico) e IL (iodofórmio, soro fisiológico e laserterapia). Os animais foram eutanasiados oito e quinze dias após a cirurgia, as peças cirúrgicas foram removidas, processadas para inclusão em parafina e os cortes histológicos corados em Azul de Toluidina 0.2%, para quantificação dos mastócitos. A análise de variância (ANOVA) e o teste de Tukey post hoc foram aplicados para determinar diferenças significativas entre os grupos quanto ao número de mastócitos (p<0.05). Resultado: Nos grupos HL, HPL e IL houve uma diminuição de mastócitos em ambos os períodos experimentais em relação aos grupos HS, HPS e IS, porém não se observou diferença estatística significativa entre o grupo HPS e o HPL aos oito dias. Conclusão: A laserterapia foi eficaz em modular a intensidade da resposta inflamatória induzida pelos medicamentos endodônticos a partir da redução significativa na quantidade de mastócitos.Descritores: Endodontia; laserterapia; mastócitos; inflamação; subcutâneo. Abstract Introduction: Endodontic medications contain toxic components that cause varying degrees of inflammation.Objective: This study evaluated the effect of laser therapy on the inflammatory response induced by intracanal medications implanted into the subcutaneous tissue of rats using a quantitative analysis of mast cells. Material and method: Polyethylene tubes containing the medications were implanted in the dorsum of 60 rats divided into six groups, including HS (P.A. calcium hydroxide paste), HL (P.A. calcium hydroxide paste and laser therapy), HPS (P.A. calcium hydroxide paste with camphorated paramonochlorophenol), HPL (P.A. calcium hydroxide paste with camphorated paramonochlorophenol and laser therapy), IS (iodoform with saline) and IL (iodoform with saline and laser therapy). The animals were euthanized eight or fifteen days after surgery, and samples were removed and embedded in paraffin. Histological sections were stained with 0.2% toluidine blue for the quantification of mast cells. Analysis of variance (ANOVA) and Tukey's post-hoc test were applied to determine significant differences in the number of mast cells between groups (p<0.05). Result: There was a decrease in mast cells for the HL, HPL and IL groups when compared with the HS, HPS and IS groups at both time points. There was no statistically significant differe...

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“…5) suggests similarity to the substrate binding profile of CPA1 and CPA6, with Ala 268 making the pocket deeper, yet Ser 253 making it shorter, resulting in exclusion of amino acids at the extremes in size. Experiments have shown CPA3 to be able to cleave the C-terminal residues of neurotensin (Leu), endothelin-1 (Trp), sarafotoxin 6b (Ile-Trp), kinetensin (Leu), Leuenkephalin (Leu), and xenopsin (Leu) (54). However, another study indicated that purified human CPA3 displayed no activity toward carboxyl-terminal Trp or Ala, but more activity than bovine CPA1 against carboxyl-terminal Leu residues and about equal activity toward Phe and Tyr residues (55), suggesting that, indeed, intermediate sized residues may be optimal.…”

Section: Discussionmentioning

confidence: 99%

Substrate Specificity of Human Carboxypeptidase A6

Lyons

Fricker

2010

Journal of Biological Chemistry

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Carboxypeptidase A6 (CPA6) is an extracellular matrixbound metallocarboxypeptidase (CP) that has been implicated in Duane syndrome, a neurodevelopmental disorder in which the lateral rectus extraocular muscle is not properly innervated. Consistent with a role in Duane syndrome, CPA6 is expressed in a number of chondrocytic and nervous tissues during embryogenesis. To better characterize the enzymatic function and specificity of CPA6 and to compare this with other CPs, CPA6 was expressed in HEK293 cells and purified. Kinetic parameters were determined using a panel of synthetic carboxypeptidase substrates, indicating a preference of CPA6 for large hydrophobic C-terminal amino acids and only very weak activity toward small amino acids and histidine. A quantitative peptidomics approach using a mixture of peptides representative of the neuropeptidome allowed the characterization of CPA6 preferences at the P1 substrate position and suggested that small and acidic P1 residues significantly inhibit CPA6 cleavage. Finally, a comparison of available kinetic data for CPA enzymes shows a gradient of specificity across the subfamily, from the very restricted specificity of CPA2 to the very broad activity of CPA4. Structural data and modeling for all CPA/B subfamily members suggests the structural basis for the unique specificities observed for each member of the CPA/B subfamily of metallocarboxypeptidases.

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Novel insights into the biological function of mast cell carboxypeptidase A

Cited by 69 publications

References 76 publications

Active Caspase-3 Is Stored within Secretory Compartments of Viable Mast Cells

Active Caspase-3 Is Stored within Secretory Compartments of Viable Mast Cells

Effect of laser therapy on the inflammatory response induced by endodontic medications implanted into the subcutaneous tissue of rats

Substrate Specificity of Human Carboxypeptidase A6

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