Evidence map›Paper›PMID 40505870›Full record

ArticleJournal of thrombosis and haemostasis : JTH2025

Deficiencies of carboxypeptidase N and carboxypeptidase B2 have opposite effects in a virulent mouse E. coli sepsis model.

Qin Zhou, Toshihiko Nishimura, Cornelis van 't Veer, Lawrence L Leung, John Morser

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of thrombosis and haemostasis : JTH, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

5 authors.

Qin ZhouDivision of Hematology, Stanford University School of Medicine, Stanford, California, USA; Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA.
Toshihiko NishimuraDivision of Hematology, Stanford University School of Medicine, Stanford, California, USA; Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA.
Cornelis van 't VeerCenter for Experimental and Molecular Medicine, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Lawrence L LeungDivision of Hematology, Stanford University School of Medicine, Stanford, California, USA; Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA.
John MorserDivision of Hematology, Stanford University School of Medicine, Stanford, California, USA; Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA. Electronic address: jmorser@stanford.edu.

Funding

FUNCTIONAL MAPPING AND PROTEIN ENGINEERING OF THROMBINR01HL057530 · NHLBI · STANFORD UNIVERSITY · PI LEUNG, LAWRENCE L · 1999 to 2013
$4.2M
NHLBI NIH HHS R01 HL057530
6 · The paper itself

Abstract

backgroundTwo basic carboxypeptidases circulate in plasma, procarboxypeptidase B2, which is activated to carboxypeptidase B2 (CPB2), and carboxypeptidase N (CPN). These enzymes inactivate complement anaphylatoxins, C3a and C5a, with high C5a being toxic.

objectivesTo test the hypothesis that these carboxypeptidases would affect Escherichia coli sepsis in mice differently because CPN is constitutively active while procarboxypeptidase B2 beeds to be locally activated.

methodsMice deficient in CPB2, CPN, or both enzymes were infected with E. coli and their health and survival was compared to wild-type mice. Clinical chemistry, complete blood count, and bacterial load were assessed.

resultsLack of CPB2 prolonged survival while lack of CPN shortened survival compared to wild-type mice. Liver damage was higher in double deficient mice that were also thrombocytopenic, and CPN-deficient mice were leukopenic. Bacterial load was higher in CPB2 and double deficient mice and lower in CPN-deficient mice.

conclusionCPN provides first-line protection against excessive C3a and C5a, accounting for the shortened survival in CPN-deficient mice in this sepsis model, despite reduced E. coli load. CPB2 serves a supportive role by primarily inactivating C3a locally. Apparently, CPB2 deficiency led to enhanced local levels of protective C3a and prolonged survival in the CPB2-deficient mice in this model, while the lack of CPN exacerbated the infection.

Indexed as

Carboxypeptidase B2Escherichia coliEscherichia coli InfectionsLysine CarboxypeptidaseSepsisAnimalsBacterial LoadDisease Models, AnimalLiverMiceMice, Inbred C57BLMice, KnockoutThrombocytopeniaVirulenceCarboxypeptidase B2Lysine Carboxypeptidasecarboxypeptidasecomplement C3acomplement C5asepsis

Identifiers

PMID40505870
PMCPMC12212749

What OpenQuestion holds

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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.