Evidence map›Paper›PMID 17375198›Full record

ArticlePloS one2007

LPS responsiveness and neutrophil chemotaxis in vivo require PMN MMP-8 activity.

Angus M Tester, Jennifer H Cox, Andrea R Connor, Amanda E Starr, Richard A Dean, Xose S Puente, Carlos López-Otín, Christopher M Overall

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PloS one, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 114 papers.

0numbers the graph read from it
0cells of the map it votes in
114citing papers in PubMed
7.0field-weighted citation impact, top 3% 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

114 citing papers in PubMed, 206 citations in OpenAlex.

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  20. Role of matrix metalloproteinase in wound healing.American journal of translational research · 2022
    Review

54 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

Angus M TesterUniversity of British Columbia Centre for Blood Research, Department of Oral Biological and Medical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Jennifer H Cox
Andrea R Connor
Amanda E Starr
Richard A Dean
Xose S Puente
Carlos López-Otín
Christopher M Overall
University of British Columbia · CAUniversidad de Oviedo · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We identify matrix metalloproteinase (MMP)-8, the polymorphonuclear (PMN) leukocyte collagenase, as a critical mediator initiating lipopolysaccharide (LPS)-responsiveness in vivo. PMN infiltration towards LPS is abrogated in Mmp8-null mice. MMP-8 cleaves LPS-induced CXC chemokine (LIX) at Ser(4)-Val(5) and Lys(79)-Arg(80). LIX bioactivity is increased upon N-terminal cleavage, enhancing intracellular calcium mobilization and chemotaxis upon binding its cognate receptor, CXCR2. As there is no difference in PMN chemotaxis in Mmp8-null mice compared with wild-type mice towards synthetic analogues of MMP-8-cleaved LIX, MMP-8 is not essential for extravasation or cell migration in collagenous matrices in vivo. However, with biochemical redundancy between MMPs 1, 2, 9, and 13, which also cleave LIX at position 4 approximately 5, it was surprising to observe such a markedly reduced PMN infiltration towards LPS and LIX in Mmp8-/- mice. This lack of physiological redundancy in vivo identifies MMP-8 as a key mediator in the regulation of innate immunity. Comparable results were found with CXCL8/IL-8 and CXCL5/ENA-78, the human orthologues of LIX. MMP-8 cleaves CXCL8 at Arg(5)-Ser(6) and at Val(7)-Leu(8) in CXCL5 to activate respective chemokines. Hence, rather than collagen, these PMN chemoattractants are important MMP-8 substrates in vivo; PMN-derived MMP-8 cleaves and activates LIX to execute an in cis PMN-controlled feed-forward mechanism to orchestrate the initial inflammatory response and promote LPS responsiveness in tissue.

Indexed as

AnimalsCell MovementChemokines, CXCChemotaxisHumansLipopolysaccharidesMatrix Metalloproteinase 8MiceMice, KnockoutNeutropeniaNeutrophilsWound HealingChemokines, CXCLipopolysaccharidesMatrix Metalloproteinase 8

Identifiers

PMID17375198
PMCPMC1819564
OpenAlexW2033671240

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.