Dataset Information

Lung Mast Cells Have a High Constitutive Expression of Carboxypeptidase A3 mRNA That Is Independent from Granule-Stored CPA3.

ABSTRACT: The mast cell granule metalloprotease CPA3 is proposed to have important tissue homeostatic functions. However, the basal CPA3 mRNA and protein expression among mast cell populations has remained poorly investigated. Using a novel histology-based methodology that yields quantitative data on mRNA and protein expression at a single-cell level, the present study maps CPA3 mRNA and protein throughout the MCT and MCTC populations in healthy skin, gut and lung tissues. MCTC cells had both a higher frequency of CPA3 protein-containing cells and a higher protein-staining intensity than the MCT population. Among the tissues, skin MCs had highest CPA3 protein intensity. The expression pattern at the mRNA level was reversed. Lung mast cells had the highest mean CPA3 mRNA staining. Intriguingly, the large alveolar MCT population, that lack CPA3 protein, had uniquely high CPA3 mRNA intensity. A broader multi-tissue RNA analysis confirmed the uniquely high CPA3 mRNA quantities in the lung and corroborated the dissociation between chymase and CPA3 at the mRNA level. Taken together, our novel data suggest a hitherto underestimated contribution of mucosal-like MCT to baseline CPA3 mRNA production. The functional consequence of this high constitutive expression now reveals an important area for further research.

SUBMITTER: Siddhuraj P

PROVIDER: S-EPMC7913381 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Lung Mast Cells Have a High Constitutive Expression of Carboxypeptidase A3 mRNA That Is Independent from Granule-Stored CPA3.

Siddhuraj Premkumar P Clausson Carl-Magnus CM Sanden Caroline C Alyamani Manar M Kadivar Mohammad M Marsal Jan J Wallengren Joanna J Bjermer Leif L Erjefält Jonas S JS

Cells 20210203 2

The mast cell granule metalloprotease CPA3 is proposed to have important tissue homeostatic functions. However, the basal CPA3 mRNA and protein expression among mast cell populations has remained poorly investigated. Using a novel histology-based methodology that yields quantitative data on mRNA and protein expression at a single-cell level, the present study maps CPA3 mRNA and protein throughout the MCT and MCTC populations in healthy skin, gut and lung tissues. MCTC cells had both a higher fre ...[more]

PMID: 33546258

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Project description:Mast cells (MCs) are granular cells of the innate immune system which develop from CD34+/CD117+ progenitors and play a role in orchestrating adaptive immune responses. They have a well-known role in allergic reactions following immunoglobulin (Ig)E-mediated activation of the cell-surface expressed IgE high-affinity receptor (Fc?RI). MCs can also respond to various other stimuli due to the expression of a variety of receptors including toll-like receptors (TLRs), immunoglobulin (IgG) receptors (Fc?R), complement receptors such as C5a (CD88) expressed by skin MCs, neuropeptides receptors including nerve growth factor receptor, (NGFR), cytokines receptors such as (IL)-1R and IL-3R, and chemokines receptors including CCR-1 and CCR-3. MCs release three groups of mediators upon degranulation differentiated according to their chemical composition, storage, and time to release. These include preformed mediators (mainly histamine, tryptase, and chymase), de novo synthesized mediators such as prostaglandin (PG)D2, leukotriene (LT)B4 and LTD4, and cytokines including IL-1?, IL-3, tumor necrosis factor (TNF)?, and transforming growth factor(TGF)-?. Emerging evidence indicates a role for IgE-independent MC activation in the late-stage asthmatic response as well as in non-allergic airway diseases including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and lung cancer. MC infiltration/activation has been reported in some, but not all, studies of lung cancer. MC-derived TNF-? possesses tumor-suppressive activity while IL-1? supports tumor progression and metastasis. In IPF lungs, an increase in density of tryptase- and chymase-positive MCs (MCTC) and overexpression of TGF-? support the fibrosis progression. MC-derived chymase activates latent TGF-? that induces the differentiation of fibroblasts to matrix-producing myofibroblasts. In summary, increasing evidence highlights a critical role of MCs in non-allergic diseases that may indicate new approaches for therapy.

Dataset Information

Lung Mast Cells Have a High Constitutive Expression of Carboxypeptidase A3 mRNA That Is Independent from Granule-Stored CPA3.

Publications

Lung Mast Cells Have a High Constitutive Expression of Carboxypeptidase A3 mRNA That Is Independent from Granule-Stored CPA3.

Similar Datasets

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