PMID- 33510372
OWN - NLM
STAT- MEDLINE
DCOM- 20210916
LR  - 20240226
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 11
IP  - 1
DP  - 2021 Jan 28
TI  - Proteolytic cleavage of HLA class II by human neutrophil elastase in pneumococcal 
      pneumonia.
PG  - 2432
LID - 10.1038/s41598-021-82212-5 [doi]
LID - 2432
AB  - Bacterial and viral respiratory infections can initiate acute lung injury and 
      acute respiratory distress syndrome. Neutrophils and their granule enzymes, 
      including neutrophil elastase, are key mediators of the pathophysiology of acute 
      respiratory failure. Although intracellular neutrophil elastase functions as a 
      host defensive factor against pathogens, its leakage into airway spaces induces 
      degradation of host connective tissue components. This leakage disrupts host 
      innate immune responses via proteolytic cleavage of Toll-like receptors and 
      cytokines. Here, we investigated whether neutrophils possess proteases that 
      cleave adaptive immune molecules. We found that expression of the human leukocyte 
      antigen (HLA) class II molecule HLA-DP beta1 was decreased in THP-1-derived 
      macrophages treated with supernatants from dead neutrophils. This decreased 
      HLA-DP beta1 expression was counteracted by treatment with neutrophil elastase 
      inhibitor, suggesting proteolytic cleavage of HLA-DP beta1 by neutrophil elastase. 
      SDS-PAGE showed that neutrophil elastase cleaved recombinant HLA-DP alpha1, -DP beta1, 
      -DQ alpha1, -DQ beta1, -DR alpha, and -DR beta1. Neutrophil elastase also cleaved HLA-DP beta1 on 
      extracellular vesicles isolated from macrophages without triggering morphological 
      changes. Thus, leakage of neutrophil elastase may disrupt innate immune 
      responses, antigen presentation, and T cell activation. Additionally, inhibition 
      of neutrophil elastase is a potential therapeutic option for treating bacterial 
      and viral pneumonia.
FAU - Domon, Hisanori
AU  - Domon H
AD  - Division of Microbiology and Infectious Diseases, Niigata University Graduate 
      School of Medical and Dental Sciences, Niigata, Japan.
FAU - Maekawa, Tomoki
AU  - Maekawa T
AD  - Division of Microbiology and Infectious Diseases, Niigata University Graduate 
      School of Medical and Dental Sciences, Niigata, Japan.
FAU - Isono, Toshihito
AU  - Isono T
AD  - Division of Microbiology and Infectious Diseases, Niigata University Graduate 
      School of Medical and Dental Sciences, Niigata, Japan.
FAU - Furuta, Kazuyuki
AU  - Furuta K
AD  - Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 
      University, Okayama, Japan.
FAU - Kaito, Chikara
AU  - Kaito C
AD  - Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 
      University, Okayama, Japan.
FAU - Terao, Yutaka
AU  - Terao Y
AD  - Division of Microbiology and Infectious Diseases, Niigata University Graduate 
      School of Medical and Dental Sciences, Niigata, Japan. 
      terao@dent.niigata-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210128
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Recombinant Proteins)
RN  - EC 3.4.21.37 (ELANE protein, human)
RN  - EC 3.4.21.37 (Leukocyte Elastase)
SB  - IM
MH  - Animals
MH  - Bronchoalveolar Lavage Fluid
MH  - Disease Models, Animal
MH  - Extracellular Vesicles/metabolism
MH  - Histocompatibility Antigens Class II/*metabolism
MH  - Humans
MH  - Leukocyte Elastase/*metabolism
MH  - Macrophages/metabolism
MH  - Mice, Inbred BALB C
MH  - Neutrophils/metabolism
MH  - Pneumonia, Pneumococcal/*metabolism
MH  - *Proteolysis
MH  - Recombinant Proteins/metabolism
MH  - Streptococcus pneumoniae/physiology
MH  - THP-1 Cells
MH  - Trachea/microbiology
MH  - Mice
PMC - PMC7843615
COIS- The authors declare no competing interests.
EDAT- 2021/01/30 06:00
MHDA- 2021/09/18 06:00
PMCR- 2021/01/28
CRDT- 2021/01/29 05:52
PHST- 2020/09/07 00:00 [received]
PHST- 2021/01/18 00:00 [accepted]
PHST- 2021/01/29 05:52 [entrez]
PHST- 2021/01/30 06:00 [pubmed]
PHST- 2021/09/18 06:00 [medline]
PHST- 2021/01/28 00:00 [pmc-release]
AID - 10.1038/s41598-021-82212-5 [pii]
AID - 82212 [pii]
AID - 10.1038/s41598-021-82212-5 [doi]
PST - epublish
SO  - Sci Rep. 2021 Jan 28;11(1):2432. doi: 10.1038/s41598-021-82212-5.