Evidence map›Paper›PMID 21742978›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2011

Processing of human protryptase in mast cells involves cathepsins L, B, and C.

Quang T Le, Gregorio Gomez, Wei Zhao, Jiang Hu, Han-Zhang Xia, Yoshihiro Fukuoka, Nobuhiko Katunuma, Lawrence B Schwartz

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.6field-weighted citation impact, top 34% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Mast Cell Biology at Molecular Level: a Comprehensive Review.Clinical reviews in allergy & immunology · 2020
    Review
  7. Article
  8. Article
  9. Mast cell proteases as pharmacological targets.European journal of pharmacology · 2016
    Review
  10. Article
  11. Review
  12. Mast cell secretory granules: armed for battle.Nature reviews. Immunology · 2014
    Review
  13. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

Quang T LeDepartment of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
Gregorio Gomez
Wei Zhao
Jiang Hu
Han-Zhang Xia
Yoshihiro Fukuoka
Nobuhiko Katunuma
Lawrence B Schwartz
Virginia Commonwealth University · USTokushima Bunri University · JP

Funding

Virus Vector Shared ResourceP30CA016059 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI Paula Daniela Bos · 1985 to 2026
$51.0M
The Effect of Lyn Deficiency on Mast Cell Activation and Inflammatory Disease ProU19AI077435 · NIAID · VIRGINIA COMMONWEALTH UNIVERSITY · PI SCHWARTZ, LAWRENCE B. · 2008 to 2012
$7.7M
DIFFERENT TYPES OF HUMAN MAST CELLSR01AI027517 · NIAID · VIRGINIA COMMONWEALTH UNIVERSITY · PI SCHWARTZ, LAWRENCE B. · 1989 to 2009
$2.2M
NCI NIH HHS P30 CA016059NIAID NIH HHS R01 AI027517NIAID NIH HHS R01-AI27517NIAID NIH HHS U19 AI077435NIAID NIH HHS U19-AI77435
6 · The paper itself

Abstract

Human β-tryptase is stored in secretory granules of human mast cells as a heparin-stabilized tetramer. β-Protryptase in solution can be directly processed to the mature enzyme by cathepsin (CTS) L and CTSB, and sequentially processed by autocatalysis at R(-3), followed by CTSC proteolysis. However, it is uncertain which CTS is involved in protryptase processing inside human mast cells, because murine bone marrow-derived mast cells from CTSC-deficient mice convert protryptase (pro-mouse mast cell protease-6) to mature mouse mast cell protease-6. This finding suggests that other proteases are important for processing human β-protryptase. In the current study, reduction of either CTSB or CTSL activity inside HMC-1 cells by short hairpin RNA silencing or CTS-specific pharmacologic inhibitors substantially reduced mature β-tryptase formation. Similar reductions of tryptase levels in primary skin-derived mast cells were observed with these pharmacologic inhibitors. In contrast, protryptase processing was minimally reduced by short hairpin RNA silencing of CTSC. A putative pharmacologic inhibitor of CTSC markedly reduced tryptase levels, suggesting an off-target effect. Skin mast cells contain substantially greater amounts of CTSL and CTSB than do HMC-1 cells, the opposite being found for CTSC. Both CTSL and CTSB colocalize to the secretory granule compartment of skin mast cells. Thus, CTSL and CTSB are central to the processing of protryptase(s) in human mast cells and are potential targets for attenuating production of mature tryptase in vivo.

Indexed as

AnimalsCathepsin BCathepsin CCathepsin LCell Line, TumorEnzyme PrecursorsHumansMast CellsMiceMice, Mutant StrainsSecretory VesiclesSkinTryptasesCathepsin BCathepsin CCathepsin LCTSB protein, humanCTSC protein, humanCTSL protein, humanEnzyme PrecursorsTpsb2 protein, mouseTryptases

Identifiers

PMID21742978
PMCPMC3150348
OpenAlexW1628501016

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.