PMID- 30557883
OWN - NLM
STAT- MEDLINE
DCOM- 20200508
LR  - 20200508
IS  - 1662-8128 (Electronic)
IS  - 1662-811X (Print)
IS  - 1662-811X (Linking)
VI  - 11
IP  - 2
DP  - 2019
TI  - Platelet-Dense Granules Worsen Pre-Infection Thrombocytopenia during 
      Gram-Negative Pneumonia-Derived Sepsis.
PG  - 168-180
LID - 10.1159/000494147 [doi]
AB  - Platelet-dense (delta) granules are important for platelet function. Platelets 
      contribute to host defense and vascular integrity during pneumonia and sepsis, 
      and delta granule products, including adenosine diphosphate (ADP), can influence 
      inflammatory responses. We therefore aimed to study the role of platelet delta 
      granules in the host response during sepsis. Hermansky-Pudlak syndrome (Hps)3coa 
      mice (with reduced delta granule content), mice treated with the platelet ADP 
      receptor inhibitor clopidogrel, and appropriate control mice were infected with 
      the human sepsis pathogen Klebsiella pneumoniae via the airways to induce 
      pneumonia and sepsis. In order to override potential redundancy in platelet 
      functions, we also studied Hps3coa and control mice with moderate 
      antibody-induced thrombocytopenia (10%) prior to infection. We found that 
      sepsis-induced thrombocytopenia tended to be less severe in Hps3coa mice, and was 
      significantly ameliorated in Hps3coa mice with low pre-infection platelet counts. 
      Bacterial growth was similar in Hps3coa and control mice in the presence of 
      normal platelet counts prior to infection, but lower in the lungs of Hps3coa mice 
      with low pre-infection platelet counts. Hps3coa mice had unaltered lung pathology 
      and distant organ injury during pneumosepsis, irrespective of pre-infection 
      platelet counts; lung bleeding did not differ between Hps3coa and control mice. 
      Clopidogrel did not influence any host response parameter. These data suggest 
      that platelet delta granules can play a detrimental role in pneumosepsis by 
      aggravating thrombocytopenia and impairing local antibacterial defense, but that 
      these unfavorable effects only become apparent in the presence of low platelet 
      counts.
CI  - (c) 2018 The Author(s) Published by S. Karger AG, Basel.
FAU - Claushuis, Theodora A M
AU  - Claushuis TAM
AD  - Center for Experimental and Molecular Medicine, Academic Medical Center, 
      University of Amsterdam, Amsterdam, The Netherlands, t.a.claushuis@amc.uva.nl.
FAU - de Vos, Alex F
AU  - de Vos AF
AD  - Center for Experimental and Molecular Medicine, Academic Medical Center, 
      University of Amsterdam, Amsterdam, The Netherlands.
FAU - Roelofs, Joris J T H
AU  - Roelofs JJTH
AD  - Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands.
FAU - de Boer, Onno J
AU  - de Boer OJ
AD  - Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands.
FAU - van 't Veer, Cornelis
AU  - van 't Veer C
AD  - Center for Experimental and Molecular Medicine, Academic Medical Center, 
      University of Amsterdam, Amsterdam, The Netherlands.
FAU - van der Poll, Tom
AU  - van der Poll T
AD  - Center for Experimental and Molecular Medicine, Academic Medical Center, 
      University of Amsterdam, Amsterdam, The Netherlands.
AD  - Division of Infectious Diseases, Academic Medical Center, University of 
      Amsterdam, Amsterdam, The Netherlands.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181217
PL  - Switzerland
TA  - J Innate Immun
JT  - Journal of innate immunity
JID - 101469471
RN  - 0 (Hps3 protein, mouse)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
SB  - IM
MH  - Animals
MH  - Blood Platelets/*immunology
MH  - Disease Models, Animal
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/genetics
MH  - Klebsiella Infections/*immunology
MH  - Klebsiella pneumoniae/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Mutant Strains
MH  - Mutation/genetics
MH  - Pneumonia, Bacterial/*immunology
MH  - Secretory Vesicles/*metabolism
MH  - Sepsis/*immunology
MH  - Thrombocytopenia/*immunology
PMC - PMC6738263
OTO - NOTNLM
OT  - Animal models
OT  - Bacterial infection
OT  - Host defense
OT  - Platelets
OT  - Sepsis
EDAT- 2018/12/18 06:00
MHDA- 2020/05/10 06:00
PMCR- 2018/12/17
CRDT- 2018/12/18 06:00
PHST- 2018/08/11 00:00 [received]
PHST- 2018/09/23 00:00 [accepted]
PHST- 2018/12/18 06:00 [pubmed]
PHST- 2020/05/10 06:00 [medline]
PHST- 2018/12/18 06:00 [entrez]
PHST- 2018/12/17 00:00 [pmc-release]
AID - 000494147 [pii]
AID - jin-0011-0168 [pii]
AID - 10.1159/000494147 [doi]
PST - ppublish
SO  - J Innate Immun. 2019;11(2):168-180. doi: 10.1159/000494147. Epub 2018 Dec 17.