U238224.pdf (15.55 MB)
Development of monocyte and macrophage subpopulations
thesisposted on 2014-12-15, 10:39 authored by Asaad Aldraihim
The mechanism by which monocytes develop into different macrophages in vivo is not well understood. This study examines the in vitro development of different types of monocytes-derived macrophages (MDM) from the two main blood monocyte subsets (CD14++ Mo and CD14+16+Mo).;Culture of CD14++Mo and CD14+16 +Mo with macrophage colony-stimulating factor (M-CSF) for 7 days generated two phenotypically and functionally different types of macrophage. The hallmark of CD14+16+MDM is the expression of CD209 (DC-SIGN), while CD14++MDM remains CD209 negative. In addition, CD14 +16+MDM show higher expression of CD14 and human leukocyte antigen-DR (HLA-DR), reflecting the ability to bind lipopolysaccharide (LPS) and for antigen presentation respectively. Moreover, alternative activation of macrophages with interleukin-13 (IL-13) led to the generation of macrophages with an almost similar phenotype.;Functional analysis of cells cultured with M-CSF revealed that a higher percentage of CD14+16+MDM were able to interact with microspheres. Looking at different mycobacteria, I found that both macrophages generated showed low ability to interact with M. chelonae and M. smegmatis. On the other hand, interaction with M. bovis Bacille-Calmette-Guerin (BCG) was strong and the number of bacteria interacting with CD14+16+MDM was higher than in CD14++MDM.;In conclusion, I succeeded in generating from the two blood monocytes subsets two different types of macrophage with distinct phenotypes. Moreover, they showed remarkably different functions with respect to their ability to interact with foreign materials. This evidence is the first to show that the type of monocytes can determine the type of macrophage generated.
Date of award2007-01-01
Author affiliationInfection immunity and inflammation
Awarding institutionUniversity of Leicester