PMID- 35163636
OWN - NLM
STAT- MEDLINE
DCOM- 20220222
LR  - 20230917
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 23
IP  - 3
DP  - 2022 Feb 2
TI  - COVID-19 and Lung Mast Cells: The Kallikrein-Kinin Activation Pathway.
LID - 10.3390/ijms23031714 [doi]
LID - 1714
AB  - Mast cells (MCs) have relevant participation in inflammatory and vascular 
      hyperpermeability events, responsible for the action of the kallikrein-kinin 
      system (KKS), that affect patients inflicted by the severe form of COVID-19. 
      Given a higher number of activated MCs present in COVID-19 patients and their 
      association with vascular hyperpermeability events, we investigated the factors 
      that lead to the activation and degranulation of these cells and their harmful 
      effects on the alveolar septum environment provided by the action of its 
      mediators. Therefore, the pyroptotic processes throughout caspase-1 (CASP-1) and 
      alarmin interleukin-33 (IL-33) secretion were investigated, along with the 
      immunoexpression of angiotensin-converting enzyme 2 (ACE2), bradykinin receptor 
      B1 (B1R) and bradykinin receptor B2 (B2R) on post-mortem lung samples from 24 
      patients affected by COVID-19. The results were compared to 10 patients affected 
      by H1N1pdm09 and 11 control patients. As a result of the inflammatory processes 
      induced by SARS-CoV-2, the activation by immunoglobulin E (IgE) and degranulation 
      of tryptase, as well as Toluidine Blue metachromatic (TB)-stained MCs of the 
      interstitial and perivascular regions of the same groups were also counted. An 
      increased immunoexpression of the tissue biomarkers CASP-1, IL-33, ACE2, B1R and 
      B2R was observed in the alveolar septum of the COVID-19 patients, associated with 
      a higher density of IgE(+) MCs, tryptase(+) MCs and TB-stained MCs, in addition 
      to the presence of intra-alveolar edema. These findings suggest the direct 
      correlation of MCs with vascular hyperpermeability, edema and diffuse alveolar 
      damage (DAD) events that affect patients with a severe form of this disease. The 
      role of KKS activation in events involving the exacerbated increase in vascular 
      permeability and its direct link with the conditions that precede intra-alveolar 
      edema, and the consequent DAD, is evidenced. Therapy with drugs that inhibit the 
      activation/degranulation of MCs can prevent the worsening of the prognosis and 
      provide a better outcome for the patient.
FAU - Nagashima, Seigo
AU  - Nagashima S
AD  - Postgraduate Program of Health Sciences, School of Medicine, Pontificia 
      Universidade Catolica do Parana, Curitiba 80910-215, Brazil.
FAU - Dutra, Anderson Azevedo
AU  - Dutra AA
AD  - Postgraduate Program of Health Sciences, School of Medicine, Pontificia 
      Universidade Catolica do Parana, Curitiba 80910-215, Brazil.
FAU - Arantes, Mayara Pezzini
AU  - Arantes MP
AD  - Postgraduate Program of Health Sciences, School of Medicine, Pontificia 
      Universidade Catolica do Parana, Curitiba 80910-215, Brazil.
FAU - Zeni, Rafaela Chiuco
AU  - Zeni RC
AD  - Postgraduate Program of Health Sciences, School of Medicine, Pontificia 
      Universidade Catolica do Parana, Curitiba 80910-215, Brazil.
FAU - Klein, Carolline Konzen
AU  - Klein CK
AUID- ORCID: 0000-0001-5452-5820
AD  - Postgraduate Program of Health Sciences, School of Medicine, Pontificia 
      Universidade Catolica do Parana, Curitiba 80910-215, Brazil.
FAU - de Oliveira, Flavia Centenaro
AU  - de Oliveira FC
AUID- ORCID: 0000-0002-6303-0720
AD  - Postgraduate Program of Health Sciences, School of Medicine, Pontificia 
      Universidade Catolica do Parana, Curitiba 80910-215, Brazil.
FAU - Piper, Giulia Werner
AU  - Piper GW
AD  - Postgraduate Program of Health Sciences, School of Medicine, Pontificia 
      Universidade Catolica do Parana, Curitiba 80910-215, Brazil.
FAU - Brenny, Isadora Drews
AU  - Brenny ID
AD  - Postgraduate Program of Health Sciences, School of Medicine, Pontificia 
      Universidade Catolica do Parana, Curitiba 80910-215, Brazil.
FAU - Pereira, Marcos Roberto Curcio
AU  - Pereira MRC
AUID- ORCID: 0000-0003-2637-8856
AD  - Postgraduate Program of Health Sciences, School of Medicine, Pontificia 
      Universidade Catolica do Parana, Curitiba 80910-215, Brazil.
FAU - Stocco, Rebecca Benicio
AU  - Stocco RB
AD  - Postgraduate Program of Health Sciences, School of Medicine, Pontificia 
      Universidade Catolica do Parana, Curitiba 80910-215, Brazil.
FAU - Martins, Ana Paula Camargo
AU  - Martins APC
AUID- ORCID: 0000-0002-6242-7099
AD  - Postgraduate Program of Health Sciences, School of Medicine, Pontificia 
      Universidade Catolica do Parana, Curitiba 80910-215, Brazil.
FAU - de Castro, Eduardo Morais
AU  - de Castro EM
AUID- ORCID: 0000-0001-6136-2660
AD  - Postgraduate Program in Biotechnology Applied in Health of Children and 
      Adolescent, Instituto de Pesquisa Pele Pequeno Principe, Faculdades Pequeno 
      Principe, Curitiba 80250-060, Brazil.
FAU - Vaz de Paula, Caroline Busatta
AU  - Vaz de Paula CB
AUID- ORCID: 0000-0002-8434-8471
AD  - Postgraduate Program of Health Sciences, School of Medicine, Pontificia 
      Universidade Catolica do Parana, Curitiba 80910-215, Brazil.
FAU - Amaral, Andrea Novaes Moreno
AU  - Amaral ANM
AUID- ORCID: 0000-0002-2730-2952
AD  - Postgraduate Program of Health Sciences, School of Medicine, Pontificia 
      Universidade Catolica do Parana, Curitiba 80910-215, Brazil.
FAU - Machado-Souza, Cleber
AU  - Machado-Souza C
AUID- ORCID: 0000-0003-0565-3492
AD  - Postgraduate Program in Biotechnology Applied in Health of Children and 
      Adolescent, Instituto de Pesquisa Pele Pequeno Principe, Faculdades Pequeno 
      Principe, Curitiba 80250-060, Brazil.
FAU - Baena, Cristina Pellegrino
AU  - Baena CP
AD  - Postgraduate Program of Health Sciences, School of Medicine, Pontificia 
      Universidade Catolica do Parana, Curitiba 80910-215, Brazil.
AD  - Marcelino Champagnat Hospital, Curitiba 80020-110, Brazil.
FAU - Noronha, Lucia
AU  - Noronha L
AUID- ORCID: 0000-0003-0310-7164
AD  - Postgraduate Program of Health Sciences, School of Medicine, Pontificia 
      Universidade Catolica do Parana, Curitiba 80910-215, Brazil.
LA  - eng
GR  - CNPq (304356/2018-2); BRDE-PUCPR/CNPq (304356/2018-2); BRDE-PUCPR/
PT  - Journal Article
DEP - 20220202
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (IL33 protein, human)
RN  - 0 (Interleukin-33)
RN  - EC 3.4.17.23 (ACE2 protein, human)
RN  - EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
RN  - EC 3.4.22.36 (Caspase 1)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Angiotensin-Converting Enzyme 2/*metabolism
MH  - Autopsy
MH  - COVID-19/immunology/*pathology/virology
MH  - *Capillary Permeability
MH  - Caspase 1/metabolism
MH  - Female
MH  - Humans
MH  - Interleukin-33/metabolism
MH  - Kallikrein-Kinin System/*physiology
MH  - Lung/immunology/metabolism/*pathology/virology
MH  - Male
MH  - Mast Cells/*immunology/metabolism/virology
MH  - Middle Aged
MH  - SARS-CoV-2/*immunology/isolation & purification/pathogenicity
PMC - PMC8836064
OTO - NOTNLM
OT  - COVID-19
OT  - edema
OT  - inflammation
OT  - kallikrein-kinin system (KKS)
OT  - mast cells (MCs)
OT  - vascular hyperpermeability
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript, or in the decision to publish the results.
EDAT- 2022/02/16 06:00
MHDA- 2022/02/23 06:00
PMCR- 2022/02/02
CRDT- 2022/02/15 01:18
PHST- 2021/12/28 00:00 [received]
PHST- 2022/01/28 00:00 [revised]
PHST- 2022/01/28 00:00 [accepted]
PHST- 2022/02/15 01:18 [entrez]
PHST- 2022/02/16 06:00 [pubmed]
PHST- 2022/02/23 06:00 [medline]
PHST- 2022/02/02 00:00 [pmc-release]
AID - ijms23031714 [pii]
AID - ijms-23-01714 [pii]
AID - 10.3390/ijms23031714 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 Feb 2;23(3):1714. doi: 10.3390/ijms23031714.