Polyamine involvement in functional activation of human macrophages

Messina, L; Spampinato, Giorgia; Arcidiacono, Antonio; Malaguarnera, Lucia; Pagano, Maria Carmen; Kamińska, Bożena; Kaczmarek, Leszek; Messina, Angelo

doi:10.1002/jlb.52.6.585

Cited by 27 publications

(18 citation statements)

References 16 publications

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“…Due to their implication in cellular processes essential for cell viability, intracellular polyamines are indispensable for the correct functioning of immune cells. In support of this notion, it has been described that polyamines are required for the appropriate differentiation of cytolytic T lymphocytes [Bowlin et al, 1987], the production of immunoglobulins by B lymphocytes [Pasquali et al, 1988] and the stimulated release of superoxide by monocytes and macrophages Messina et al, 1992]. On the other hand, there is evidence indicating that polyamines may play an inhibitory role in certain immune functions.…”

Section: Discussionmentioning

confidence: 91%

Polyamines affect histamine synthesis during early stages of IL‐3‐induced bone marrow cell differentiation

Garcia-Faroldi

Correa‐Fiz

Abrighach

et al. 2009

J of Cellular Biochemistry

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Mast cells synthesize and store histamine, a key immunomodulatory mediator. Polyamines are essential for every living cell. Previously, we detected an antagonistic relationship between the metabolisms of these amines in established mast cell and basophilic cell lines. Here, we used the IL-3-driven mouse bone marrow-derived mast cell (BMMC) culture system to further investigate this antagonism in a mast cell model of deeper physiological significance. Polyamines and histamine levels followed opposite profiles along the bone marrow cell cultures leading to BMMCs. alpha-Difluoromethylornithine (DFMO)-induced polyamine depletion resulted in an upregulation of histidine decarboxylase (HDC, the histamine-synthesizing enzyme) expression and activity, accompanied by increased histamine levels, specifically during early stages of these cell cultures, where an active histamine synthesis process occurs. In contrast, DFMO did not induce any effect in either HDC activity or histamine levels of differentiated BMMCs or C57.1 mast cells, that exhibit a nearly inactive histamine synthesis rate. Sequence-specific DNA methylation analysis revealed that the DFMO-induced HDC mRNA upregulation observed in early bone marrow cell cultures is not attributable to a demethylation of the gene promoter caused by the pharmacological polyamine depletion. Taken together, the results support an inverse relationship between histamine and polyamine metabolisms during the bone marrow cell cultures leading to BMMCs and, moreover, suggest that the regulation of the histamine synthesis occurring during the early stages of these cultures depends on the concentrations of polyamines.

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Section: Discussionmentioning

confidence: 91%

Polyamines affect histamine synthesis during early stages of IL‐3‐induced bone marrow cell differentiation

Garcia-Faroldi

Correa‐Fiz

Abrighach

et al. 2009

J of Cellular Biochemistry

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“…Cationized albumin is more actively internalized by macrophages than untreated albumin and anionic sugars of the macrophage surface were identified as the binding site for cationic molecules [6]. This effect of cationic molecules on macrophage biology was supported by the observation that polyamines are efficient activators of macrophage function [7].The explanation of the stimulatory effect of cationic molecules on macrophage function is not clear. Bacterial cells with sialic or polysialic acid anionic coat are only poor activators of complement, and the ability of macrophages to engulf and kill these bacteria is minimal [8].…”

mentioning

confidence: 86%

Effect of cationic groups on the adhesivity of peritoneal macrophages to polymeric beads

Smetana

Jelı́nková

Vacı́k

et al. 1995

J Mater Sci: Mater Med

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This study demonstrates the adhesion of macrophages to polymer beads from a copolymer of hydroxyethyl methacrylate and dimethyl aminoethyl methacrylate intraperitoneally injected into the rat. Dimethyl aminoethyl methacrylate exhibited a stimulatory effect on macrophage adhesion 5 h after injection of the beads. Electron microscopy demonstrated protein adsorption on the surface of the beads. Protein fibres between the cell surface and beads were observed. The experimental system used minimizes the influence of tissue damage at macrophage recognition of polymers. This method seems to be suitable for short-term investigation of macrophage-polymer interaction. IntroductionThe chemical structure of polymers, and especially their surface properties, strongly influence their biological properties, including the effect on macrophages behaviour [1,2]. Our previous studies demonstrated a remarkable effect of the functional chemical groups in certain polymeric matrices on the adhesion, spreading and fusion of macrophages on the surface of subcutaneously implanted polymers. Anionic groups were found to have an inhibitory influence on these parameters (-COOH >-SO3H ) while cationic groups stimulate macrophage fusion [3][4][5]. Cationized albumin is more actively internalized by macrophages than untreated albumin and anionic sugars of the macrophage surface were identified as the binding site for cationic molecules [6]. This effect of cationic molecules on macrophage biology was supported by the observation that polyamines are efficient activators of macrophage function [7].The explanation of the stimulatory effect of cationic molecules on macrophage function is not clear. Bacterial cells with sialic or polysialic acid anionic coat are only poor activators of complement, and the ability of macrophages to engulf and kill these bacteria is minimal [8]. These bacterial strains are usually highly pathogenic, in contrast to the unsialiled strains of the same species.Our previous studies with subcutaneously implanted polymers were able to demonstrate only the relatively late response, because the early observations were influenced by surgical trauma [3][4][5]. This paper considers the behaviour during the first 5 h after intraperitoneal injection of beads of a copolymer containing an increased concentration of dimethyl amino-

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“…The SIVE study suggests that even though low concentrations of natural polyamines are present in the blood (64,65), sufficient amounts of MGBG are getting into macrophages in vivo and most importantly into the CNS to mediate significant macrophage-targeted effects. In addition to the activity against HIV described here, MGBG has been shown to inhibit macrophage activation mediated by type I macrophage activators, such as tumor necrosis factor alpha (TNF-␣), gamma interferon, and lipopolysaccharide (LPS) (41,42). Considering the importance of inflammation in the pathogenesis of HAND and atherosclerosis driven in a large part by HIV-infected macrophages, the use of MGBG provides an approach against both HIV infection and the associated pathogenic inflammation.…”

Section: Figmentioning

confidence: 86%

“…Polyamines are required for cell proliferation and differentiation in general (36,37). Since fully differentiated and activated macrophages appear to be targets for HIV infection (38)(39)(40) and MGBG was reported to interfere with macrophage activation in vitro (41,42), we evaluated MGBG for its ability to interfere with HIV infection in primary macrophages.…”

mentioning

confidence: 99%

Inhibition of HIV Expression and Integration in Macrophages by Methylglyoxal-Bis-Guanylhydrazone

Jin

McGrath

2015

J Virol

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Macrophages are a target for infection with HIV and represent one of the viral reservoirs that are relatively resistant to current antiretroviral drugs. Here we demonstrate that methylglyoxal-bis-guanylhydrazone (MGBG), a polyamine analog and potent S-adenosylmethionine decarboxylase inhibitor, decreases HIV expression in monocytes and macrophages. MGBG is selectively concentrated by these cells through a mechanism consistent with active transport by the polyamine transporter. Using a macrophage-tropic reporter virus tagged with the enhanced green fluorescent protein, we demonstrate that MGBG decreases the frequency of HIV-infected cells. The effect is dose dependent and correlates with the production of HIV p24 in culture supernatants. This anti-HIV effect was further confirmed using three macrophage-tropic primary HIV isolates. Viral life cycle mapping studies show that MGBG inhibits HIV DNA integration into the cellular DNA in both monocytes and macrophages. O ne of the major remaining obstacles in treating human immunodeficiency type 1 (HIV-1)-related diseases is the elimination of viral reservoirs that contribute to persistent infection and chronic immune activation. Although highly active antiretroviral therapy (HAART) is effective at reducing the plasma viral load and slowing down the decline of CD4 ϩ T lymphocytes and dendritic cells, it has failed to eradicate the residual long-lived HIV-infected cellular reservoirs (1-3). At the molecular level, HAART successfully suppresses HIV RNA replication and decreases total viral DNA load in treated individuals. However, it fails to eliminate the integrated proviral DNA (4, 5). Even in HAART-treated patients with an undetectable plasma viral load, discontinuation of treatment is routinely associated with the reappearance of HIV RNA in circulation, confirming the presence of significant HIV proviral reservoirs in HAART-treated individuals (6, 7).HIV-1 cellular reservoirs include resting CD4 ϩ T lymphocytes and cells of the monocyte and macrophage lineage (1, 8, 9). Research on the HIV reservoirs has largely focused on T cells and more specifically a rare subset of resting memory CD4 T cells that has been reproducibly identified in the blood of patients with low or no detectible plasma viral loads (10). Cells of the monocyte and macrophage lineage may represent another mechanism for viral persistence. These cells are among the cells infected early upon exposure to HIV (11), and the presence of CCR5-utilizing "macrophage-tropic" forms of HIV in the plasma of essentially all newly infected individuals is consistent with the notion that macrophages represent an early target for HIV infection (12)(13)(14)(15). In contrast to CD4 T cells which die with effective HIV replication, macrophages are resistant to the cytopathic effect of the virus. Furthermore, macrophages and dendritic cells are capable of transmitting HIV to T cells or other macrophages via cell-cell contact (16). Depending on the origins of the virus, both cis-infection and trans-infection modes h...

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Polyamine involvement in functional activation of human macrophages

Cited by 27 publications

References 16 publications

Polyamines affect histamine synthesis during early stages of IL‐3‐induced bone marrow cell differentiation

Polyamines affect histamine synthesis during early stages of IL‐3‐induced bone marrow cell differentiation

Effect of cationic groups on the adhesivity of peritoneal macrophages to polymeric beads

Inhibition of HIV Expression and Integration in Macrophages by Methylglyoxal-Bis-Guanylhydrazone

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