<b>Granulocyte–macropha ge colony‐stimulating factor down‐regulates CD14 expression on monocytes</b>

Kruger, Mariana; Winkel, Jan G. J. van de; Wit, T. P. M. De; Coorevits, Lieve; Ceuppens, Jan L.

doi:10.1046/j.1365-2567.1996.d01-707.x

Cited by 30 publications

(36 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Survival rates of differentiated macrophages varied in the following order: GM-CSF Ͼ M-CSF Ͼ hAB (from 80 to 50%, respectively). Cell surface marker analysis on day 4 macrophages showed a decrease in CD14 surface labeling in macrophages differentiated in GM-CSF, as compared to the starting monocyte population and to macrophages differentiated under the remaining conditions, as reported previously (Table 1) (16,17). Macrophages differentiated under the three conditions, however, had similar functional properties (as determined by phagocytosis and mixed lymphocyte reaction; data not shown).…”

Section: Fig 5 Comparison Between Moloney MLV Andsupporting

confidence: 85%

Transduction of Nondividing Human Macrophages with Gammaretrovirus-Derived Vectors

Jarrosson-Wuillème

Goujon

Bernaud³

et al. 2006

J Virol

View full text Add to dashboard Cite

It is commonly accepted that infection of nondividing cells by gammaretroviruses such as the murine leukemia viruses is inefficient due to their inability to cross the nuclear envelope barrier. Challenging this notion, we now show that human nondividing macrophages display a specific window of susceptibility to transduction with a Friend murine leukemia virus (F-MLV)-derived vector during their differentiation from monocytes. This finding suggests that factors other than the nuclear membrane govern permissiveness to gammaretroviral infection and raises the possibility of using the macrophage tropism of F-MLV in gene therapy.The nuclear envelope poses itself as a barrier between the initial and final phases of the early steps of retroviral infection: that is, between viral genome entry into the cytoplasm and its integration into the host genome in the nucleus. Two basic mechanisms have been proposed for the passage of viral nucleoprotein complexes (called reverse transcription or preintegration complexes [RTCs and PICs, respectively]) (3,7,8,25) through the nuclear membrane: active import through the nuclear pores or passive passage in the nucleus following nuclear membrane disassembly during mitosis. Active nuclear import can occur either through hijacking of the normal cytonucleoplasmic transport machinery or through the induction of distortions that perturb the integrity of the nuclear envelope, as proposed for the human immunodeficiency virus type 1 (HIV-1) Vpr protein (5).Among Retroviridae, lentiviruses such as HIV-1 have developed probably the most efficient way to traverse an intact nuclear membrane, and this results in the broad tropism of HIV-derived lentiviral vectors for most nondividing cells. Although the exact mechanism by which this is accomplished remains to be elucidated, lentiviral PICs appear to be gated through the nuclear pore and a number of viral proteins that compose it have nucleophilic properties, like Vpr, matrix (MA), and integrase (IN). An additional signal for nuclear transport may be provided by a particular single-gap structure determined by the central polypurine tract (cPPT) present on double-stranded proviral DNA (43). However, no consensus has yet been formed as to the importance of each of these elements in driving viral nuclear import. MA, Vpr, and cPPT can be deleted without completely abolishing either nuclear entry or viral infection (6, 9, 30), and the role played by IN nuclear localization signals is still being debated (6).If nuclear localization of certain PIC components is taken as evidence suggesting-but not proving-they may concur in driving the entire viral nucleoprotein complex inside the nucleus, then the ability to infect nondividing cells should hardly be restricted to lentiviruses. Simple retroviruses previously referred to as "oncoretroviruses" should share a similar theoretical ability. For instance, the INs of certain alpharetroviruses are localized in the nucleus (18,19,39), and for gammaretroviruses such as the murine leukemia virus (MLV), clear evidence...

show abstract

Section: Fig 5 Comparison Between Moloney MLV Andsupporting

confidence: 85%

Transduction of Nondividing Human Macrophages with Gammaretrovirus-Derived Vectors

Jarrosson-Wuillème

Goujon

Bernaud³

et al. 2006

J Virol

View full text Add to dashboard Cite

show abstract

“…As 2 O 3 also decreased expression of CD71, a well-known macrophagic differentiation marker (18). In contrast, it markedly increased that of CD14, a typical marker of human blood monocytes, down-regulated by GM-CSF during macrophagic differentiation (26). However, a concentration of 1 M As 2 O 3 failed to modify CD11c levels, which indicates that metalloid effects were not due to a general alteration of surface markers.…”

Section: As 2 O 3 Alters Phenotype Of Human Macrophagesmentioning

confidence: 86%

Human Macrophages Constitute Targets for Immunotoxic Inorganic Arsenic

Lemarié

Morzadec

Bourdonnay

et al. 2006

The Journal of Immunology

125

View full text Add to dashboard Cite

Chronic exposure to inorganic arsenic, a widely distributed environmental contaminant, can lead to toxic effects, including immunosuppression. Owing to the established roles of human macrophages in immune defense, we determined, in the present study, whether inorganic arsenic can affect these major immune cells. Our results demonstrate that noncytotoxic concentrations of arsenic trioxide (As2O3), an inorganic trivalent form, markedly impair differentiated features of human blood monocyte-derived macrophages. First, treatment of macrophages with 1 μM As2O3 induced a rapid cell rounding and a subsequent loss of adhesion. These morphologic alterations were associated with a marked reorganization of actin cytoskeleton, which includes retraction of peripheral actin extensions and formation of a cortical actin ring. In addition, As2O3 reduced expression of various macrophagic surface markers, enhanced that of the monocytic marker CD14, and altered both endocytosis and phagocytosis; unexpectedly, exposure of macrophages to the metalloid also strongly potentiated expression of TNFα and IL-8 induced by LPS. Finally, like monocytes, As2O3-treated macrophages can be differentiated into dendritic-like cells. Impairment of macrophage function by As2O3 mainly resulted from activation of a RhoA/Rho-associated kinase pathway; indeed, pretreatment of macrophages with the Rho-associated kinase inhibitor Y-27632 prevented metalloid effects on cytoskeleton and phagocytosis. Moreover, As2O3 was found to increase level of the active GTP-bound form of RhoA and that of phosphorylated-Moesin, a major cytoskeleton adaptor protein involved in RhoA regulation. Taken together, our results demonstrated that human macrophages constitute sensitive targets of inorganic arsenic, which may contribute to immunotoxicity of this environmental contaminant.

show abstract

“…We and others have shown that neonatal monocytes are phenotypically less mature than adult monocytes (28). Down-regulation of CD14 expression might represent a rapid adaptation of the host to stress (11). Hence, slower downregulation of CD14 expression in cord blood implies that the ability of adaptation to stress of CBMC is less than that of adult monocytes when challenged.…”

Section: Cd4mentioning

confidence: 86%

“…GM-CSF is a well-known stimulus for the activation, differentiation, and survival of monocytes. GM-CSF can reduce the CD14 expression of PBMC after 3 d of culture (11). When monocytes were cultured for 7 d with GM-CSF and serum, CD14 was, however, up-regulated, leading to a higher sensitivity toward LPS stimulation (31).…”

Section: Cd4mentioning

confidence: 98%

Changes of CD14 and CD1a Expression in Response to IL-4 and Granulocyte-Macrophage Colony-Stimulating Factor Are Different in Cord Blood and Adult Blood Monocytes

Liu

Law

et al. 2001

Pediatr Res

View full text Add to dashboard Cite

Neonates are relatively immature in their immune response; thus, to further clarify the differences of monocyte function and differentiation between neonates and adults, we investigated their CD14 ϩ CD4 ϩ and CD14 ϩ CD16 ϩ monocyte subpopulations, production of IL-1␤ and tumor necrosis factor-␣ induced by lipopolysaccharide, and their CD14 and CD1a phenotypic changes in response to IL-4 and granulocyte-macrophage colony-stimulating factor. Our results showed that 1) the expression of CD14 in cord blood monocytes was significantly lower than that in adult peripheral blood monocytes; 2) both the percentages of CD14 ϩ CD4 ϩ cells and CD14 ϩ CD16 ϩ cells among CD14 ϩ monocytes were also significantly lower in cord blood; 3) after stimulation by lipopolysaccharide for 72 h, production of both IL-1␤ and tumor necrosis factor-␣ was lower in cord blood than that in adult peripheral blood; and 4) in response to IL-4 or GM-CSF, the phenotype development of CD14 and CD1a in cord blood and adult peripheral blood was different. Downregulation of CD14 expression in response to IL-4 and GM-CSF was slower in cord blood monocytes than that in adult peripheral blood monocytes. After 9 d of culture in the presence of IL-4 and GM-CSF, the percentage of CD1a ϩ monocytes was significantly more increased in cord blood than that in adult peripheral blood. The reduced expression of CD14 and other mature phenotype markers such as CD16 and CD4 as well as the reduced IL-1␤ and tumor necrosis factor-␣ production may contribute to the impaired immune response of neonates. Slower down-regulation of CD14 by IL-4 and GM-CSF suggests that differential properties of cord blood monocytes in response to cellular stress signals take a longer time than those of adult peripheral blood monocytes. The monocyte plays an important role in host immunity. CD14, a glycoprotein of 55 kD present on most monocytes and tissue macrophages, is regarded as the most important myeloid differentiation antigen (1, 2). Functionally, CD14 acts as a receptor for the complex of LPS and LPS-binding protein (3), and mediates the response to LPS, such as the LPS-induced production of the cytokines TNF-␣, 4). The apoptosis of monocytes is associated with the down-regulation of CD14 expression (5), and CD14 is also a major receptor on phagocytes, which are involved in uptake of apoptotic cells (6). The expression of CD14 on PBMC is increased by LPS (7, 8) and decreased by IL-4 and GM-CSF (9 -11). In vitro, with CD14 down-regulation in response to IL-4 and GM-CSF, CD14ϩ monocytes can differentiate into cells displaying features of immature DC, which express CD1a (12).The heterogeneity of human PBMC in terms of size, function, and antigen expression has been reported (13,14). About 10% of the CD14 ϩ monocytes in peripheral blood express CD16, which is an Fc␥3 receptor (14, 15). The CD14 ϩ CD16 ϩ population represents more-mature monocytes and has higher antigen-presenting ability but lower phagocytic activity (16). Another antigen, CD4, is also expressed on a subpopulation of mon...

show abstract

Granulocyte–macropha ge colony‐stimulating factor down‐regulates CD14 expression on monocytes

Cited by 30 publications

References 41 publications

Transduction of Nondividing Human Macrophages with Gammaretrovirus-Derived Vectors

Transduction of Nondividing Human Macrophages with Gammaretrovirus-Derived Vectors

Human Macrophages Constitute Targets for Immunotoxic Inorganic Arsenic

Changes of CD14 and CD1a Expression in Response to IL-4 and Granulocyte-Macrophage Colony-Stimulating Factor Are Different in Cord Blood and Adult Blood Monocytes

Contact Info

Product

Resources

About