Macrophages: the overlooked target for pulmonary fibrosis and COPD

Carian Eline Boorsma

Macrophages: the overlooked target for pulmonary fibrosis and COPD

Carian Eline Boorsma

Farmacokinetiek, Toxicologie en Targeting

Onderzoeksoutput

1956 Downloads (Pure)

Samenvatting

Macrofagen zijn immuuncellen die in grote getalen in de longen aanwezig zijn om een eerstelijns verdediging te vormen tegen ingeademde bedreigingen. Om de longen te beschermen tegen de vele verschillende bedreigingen, maken macrofagen stoffen die indringers neutraliseren, maar die ook schade aan het eigen longweefsel kunnen veroorzaken. Om blijvende schade te voorkomen, stimuleren macrofagen daarom ook weefselherstel en remmen ontstekingen. Als deze functies echter niet goed op elkaar afgestemd worden, kunnen er veranderingen in het longweefsel ontstaan die bijdragen aan het ontwikkelen van ziekten als chronisch obstructief longlijden (COPD) of longfibrose.

Bij COPD dragen macrofagen bij aan het afbreken van weefsel dat alle cellen in de longen verbindt, het zogenoemde bindweefsel, waardoor er longweefsel verloren gaat. Bij longfibrose, daarentegen, stimuleren macrofagen juist de aanmaak van teveel bindweefsel waardoor de longen heel stijf worden en ademen moeilijk wordt. In verschillende studies hebben we macrofagen en hun functies gekarakteriseerd bij patiënten met COPD of longfibrose en vergeleken met macrofagen van controle-individuen. Deze kennis is vervolgens gebruikt om bepaalde functies van macrofagen te veranderen om vast te stellen of dit mogelijk therapieën zouden kunnen zijn voor een toekomstige behandeling van COPD of longfibrose.

Door onze studies weten we nu dat het systeem dat de hoeveelheid bindweefsel in botten reguleert, ook aanwezig is in de longen. Deze nieuwgevonden paralellen tussen bot en long kunnen bijdragen aan het ontwikkelen van nieuwe, macrofaag-georiënteerde geneesmiddelen tegen COPD en longfibrose. Daarnaast kan deze kennis bijdragen aan de ontwikkeling van nieuwe biomarkers die iets zeggen over het verloop van deze ziekten.

Originele taal-2	English
Kwalificatie	Doctor of Philosophy
Toekennende instantie	Rijksuniversiteit Groningen
Begeleider(s)/adviseur	Melgert, Barbro, Supervisor Timens, Wim, Supervisor Poelstra, Klaas, Supervisor
Datum van toekenning	2-nov.-2016
Plaats van publicatie	[Groningen]
Uitgever	Rijksuniversiteit Groningen
Gedrukte ISBN's	978-90-367-9328-5
Elektronische ISBN's	978-90-367-9327-8
Status	Published - 2016

Toegang tot document

Title and contents Final publisher's version, 395 KB
Chapter 1Final publisher's version, 588 KB
Chapter 2Final publisher's version, 997 KB
Chapter 3Final publisher's version, 779 KB
Chapter 4Final publisher's version, 674 KB
Chapter 5Final publisher's version, 661 KB
Chapter 6Final publisher's version, 312 KB
Chapter 7Final publisher's version, 798 KB
Chapter 8Final publisher's version, 434 KB
Complete thesisFinal publisher's version, 3,55 MB
PropositionsFinal publisher's version, 68,6 KB
movie1vehicleFinal publisher's version, 1,42 MB
Movie2ranklFinal publisher's version, 3,45 MB
Movie3inhibitorFinal publisher's version, 1,85 MB
Movie4ranklandinhibitorFinal publisher's version, 2,38 MB

Handle.net

Permanente koppeling

Citeer dit

@phdthesis{7ed7e538bf47468c9356866126b66911,

title = "Macrophages: the overlooked target for pulmonary fibrosis and COPD",

abstract = "Macrophages are important immune cells in the lungs that are a first line of defense against inhaled threats. To fulfill this protective function, macrophages produce toxic molecules that neutralize inhaled threats but these can also cause damage to lung tissue. To prevent lasting damage, macrophages stimulate tissue repair and dampen inflammation. Improper control of these diverse functions is harmful to the lungs and contributes to diseases like chronic obstructive pulmonary disease (COPD) and lung fibrosis. In COPD, macrophages contribute to the degradation of the tissue that connects all lung cells, i.e. connective tissue, leading to loss of lung tissue. In lung fibrosis, on the other hand, macrophages stimulate the production of connective tissue, which makes the lungs stiff and impairs breathing. We have characterized and investigated lung macrophages and their functions from patients with COPD or lung fibrosis and compared them to macrophages of control individuals. This knowledge was subsequently used to test experimental macrophage function-modifying therapies for the possible treatment of COPD or lung fibrosis.Our studies revealed that a system known to regulate the amount of connective tissue in bone is also present in lung tissue. This novel parallel between bone and lung will help us to design macrophage-modifying drugs that may be used for the treatment of COPD or lung fibrosis. In addition, this knowledge can contribute to the development of biomarkers that may be used to follow the course of these diseases.",

author = "Boorsma, \{Carian Eline\}",

year = "2016",

language = "English",

isbn = "978-90-367-9328-5",

publisher = "Rijksuniversiteit Groningen",

school = "University of Groningen",

}

TY - BOOK

T1 - Macrophages: the overlooked target for pulmonary fibrosis and COPD

AU - Boorsma, Carian Eline

PY - 2016

Y1 - 2016

N2 - Macrophages are important immune cells in the lungs that are a first line of defense against inhaled threats. To fulfill this protective function, macrophages produce toxic molecules that neutralize inhaled threats but these can also cause damage to lung tissue. To prevent lasting damage, macrophages stimulate tissue repair and dampen inflammation. Improper control of these diverse functions is harmful to the lungs and contributes to diseases like chronic obstructive pulmonary disease (COPD) and lung fibrosis. In COPD, macrophages contribute to the degradation of the tissue that connects all lung cells, i.e. connective tissue, leading to loss of lung tissue. In lung fibrosis, on the other hand, macrophages stimulate the production of connective tissue, which makes the lungs stiff and impairs breathing. We have characterized and investigated lung macrophages and their functions from patients with COPD or lung fibrosis and compared them to macrophages of control individuals. This knowledge was subsequently used to test experimental macrophage function-modifying therapies for the possible treatment of COPD or lung fibrosis.Our studies revealed that a system known to regulate the amount of connective tissue in bone is also present in lung tissue. This novel parallel between bone and lung will help us to design macrophage-modifying drugs that may be used for the treatment of COPD or lung fibrosis. In addition, this knowledge can contribute to the development of biomarkers that may be used to follow the course of these diseases.

AB - Macrophages are important immune cells in the lungs that are a first line of defense against inhaled threats. To fulfill this protective function, macrophages produce toxic molecules that neutralize inhaled threats but these can also cause damage to lung tissue. To prevent lasting damage, macrophages stimulate tissue repair and dampen inflammation. Improper control of these diverse functions is harmful to the lungs and contributes to diseases like chronic obstructive pulmonary disease (COPD) and lung fibrosis. In COPD, macrophages contribute to the degradation of the tissue that connects all lung cells, i.e. connective tissue, leading to loss of lung tissue. In lung fibrosis, on the other hand, macrophages stimulate the production of connective tissue, which makes the lungs stiff and impairs breathing. We have characterized and investigated lung macrophages and their functions from patients with COPD or lung fibrosis and compared them to macrophages of control individuals. This knowledge was subsequently used to test experimental macrophage function-modifying therapies for the possible treatment of COPD or lung fibrosis.Our studies revealed that a system known to regulate the amount of connective tissue in bone is also present in lung tissue. This novel parallel between bone and lung will help us to design macrophage-modifying drugs that may be used for the treatment of COPD or lung fibrosis. In addition, this knowledge can contribute to the development of biomarkers that may be used to follow the course of these diseases.

M3 - Thesis fully internal (DIV)

SN - 978-90-367-9328-5

PB - Rijksuniversiteit Groningen

CY - [Groningen]

ER -

Macrophages: the overlooked target for pulmonary fibrosis and COPD

Samenvatting

Toegang tot document

Handle.net

Vingerafdruk

Citeer dit