SwePub
Tyck till om SwePub Sök här!
Sök i LIBRIS databas

  Extended search

WFRF:(Nielsen Finn Cilius)
 

Search: WFRF:(Nielsen Finn Cilius) > Papillon-Lefevre sy...

Papillon-Lefevre syndrome patient reveals species-dependent requirements for neutrophil defenses

Sørensen, Ole E (author)
Lund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine
Clemmensen, Stine N. (author)
Dahl, Sara L. (author)
show more...
Ostergaard, Ole (author)
Heegaard, Niels H. (author)
Glenthoj, Andreas (author)
Nielsen, Finn Cilius (author)
Borregaard, Niels (author)
show less...
 (creator_code:org_t)
2014
2014
English.
In: Journal of Clinical Investigation. - 0021-9738. ; 124:10, s. 4539-4548
  • Journal article (peer-reviewed)
Abstract Subject headings
Close  
  • Papillon-Lefevre syndrome (PLS) results from mutations that inactivate cysteine protease cathepsin C (CTSC), which processes a variety of serine proteases considered essential for antimicrobial defense. Despite serine protease-deficient immune cell populations, PLS patients do not exhibit marked immunodeficiency. Here, we characterized a 24-year-old woman who had suffered from severe juvenile periodontal disease, but was otherwise healthy, and identified a homozygous missense mutation in CTSC indicative of PLS. Proteome analysis of patient neutrophil granules revealed that several proteins that normally localize to azurophil granules, including the major serine proteases, elastase, cathepsin G, and proteinase 3, were absent. Accordingly, neutrophils from this patient were incapable of producing neutrophil extracellular traps (NETs) in response to ROS and were unable to process endogenous cathelicidin hCAP-18. into the antibacterial peptide LL-37 in response to ionomycin. In immature myeloid cells from patient bone marrow, biosynthesis of CTSC and neutrophil serine proteases appeared normal along with initial processing and sorting to cellular storage. In contrast, these proteins were completely absent in mature neutrophils, indicating that CTSC mutation promotes protease degradation in more mature hematopoietic subsets, but does not affect protease production in progenitor cells. Together, these data indicate CTSC protects serine proteases from degradation in mature immune cells and suggest that neutrophil serine proteases are dispensable for human immunoprotection.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Infectious Medicine (hsv//eng)

Publication and Content Type

art (subject category)
ref (subject category)

Find in a library

To the university's database

Search outside SwePub

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Close

Copy and save the link in order to return to this view