• chemokines
• atherosclerosis

• Animals
• Lipogenesis/genetics
• Atherosclerosis/metabolism
• Atherosclerosis/pathology
• Atherosclerosis/genetics
• Mice
• Liver/metabolism
• Liver/pathology
• Receptors, CXCR4/metabolism
• Humans
• Macrophage Migration-Inhibitory Factors/metabolism
• Macrophage Migration-Inhibitory Factors/genetics
• Male
• Intramolecular Oxidoreductases/metabolism
• Intramolecular Oxidoreductases/genetics
• Chemokines/metabolism
• Chemokines/genetics
• Mice, Inbred C57BL
• Mice, Knockout, ApoE
• Antigens, Differentiation, B-Lymphocyte/metabolism
• Signal Transduction
• Hepatocytes/metabolism
• Mice, Knockout
• Apolipoproteins E/genetics
• Histocompatibility Antigens Class II

• Antimicrobial peptide
• Lipopeptide
• Multi-epitope vaccine
• Pluronic
• Poloxamer

• membrane structure and assembly
• chemistry

• Anti-Bacterial Agents/pharmacology
• Anti-Bacterial Agents/chemistry
• Molecular Dynamics Simulation
• Cell Membrane/drug effects
• Lipopolysaccharides/pharmacology
• Microbial Sensitivity Tests
• Peptides/chemistry
• Peptides/pharmacology
• Microscopy, Electron
• Gram-Negative Bacteria/drug effects
• Escherichia coli/drug effects

• CZ.02.1.01/0.0/0.0/18_046/0015974 EC | European Regional Development Fund (Europski Fond za Regionalni Razvoj)
• This work was funded by the Momentum Program (LP2016-2 and LP2021-28) of the Hungarian Academy of Sciences, the National Competitiveness and Excellence Program (NVKP_16-1-2016-0007), the BIONANO_GINOP-2.3.2-15-2016-00017 project, and the National Research, Development and Innovation Office, Hungary (TKP2021-EGA-31, 2020-1.1.2-PIACI-KFI-2020-00021, 2019-2.1.11-TÉT-2019-00091, KKP_22 Project n.o. 144180, K131594 for J.M., K124900, K137940 for A.B., K142904 for Sz.B., and K138318 to J.T.). Support from Eötvös Loránd Research Network, Grant Nos. SA-87/2021 and KEP-5/2021, are also acknowledged. A.W. and Z.V. were supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences. The authors acknowledge support from ELTE Thematic Excellence Programme 2020, the Szint+ Program, National Challenges Subprogramme-TKP2020-NKA-06. CIISB, Instruct-CZ Centre of Instruct-ERIC EU consortium, funded by MEYS CR infrastructure project LM2018127, LM2023042 and European Regional Development Fund-Project „UP CIISB“ (No. CZ.02.1.01/0.0/0.0/18_046/0015974), is gratefully acknowledged for the financial support of the measurements at the CF Cryo-Electron Microscopy and Tomography.

• cancer cells
• macrophages
• matrix
• three-dimensional (3D) coculture models

• Animals
• Coculture Techniques
• Macrophages/metabolism
• Macrophages/pathology
• Cell Line
• Neoplasms
• Phenotype
• Tumor Microenvironment

• cross-coupling
• microwave chemistry
• phosphorylation
• synthetic methods

• K 134318 National Research, Development and Innovation Office

• Humans
• Animals
• Mice
• Mycobacterium tuberculosis
• Leukocytes, Mononuclear
• Antigens, Bacterial
• CD4-Positive T-Lymphocytes
• Tuberculosis/prevention & control
• Tuberculosis Vaccines
• CD8-Positive T-Lymphocytes
• Epitopes, T-Lymphocyte
• Peptides

• H2020 Marie Sklodowska-Curie Actions
• National Laboratories Excellence program
• National Research, Development and Innovation Office
• Magyar Tudományos Akadémia
• Austrian Science Fund

Uptake of apoptotic cells induces a tolerogenic phenotype in phagocytes and promotes peripheral tolerance. The highly conserved Annexin core domain, present in all members of the Annexin family, becomes exposed on the apoptotic cell-surface and triggers tolerogenic signalling in phagocytes via the Dectin-1 receptor. Consequently, Annexins exposed on tumour cells upon cell death are expected to induce tolerance towards tumour antigens, inhibiting tumour rejection.

Expression analysis for all Annexin family members was conducted in cancer cell lines of diverse origins. Presentation of Annexins on the cell surface during apoptosis of cancer cell lines was investigated using surface washes and immunoblotting. Expression data from the GEO database was analysed to compare Annexin levels between malignant and healthy tissue.

Six Annexins at least were consistently detected on mRNA and protein level for each investigated cell line. AnxA1, AnxA2 and AnxA5 constituted the major part of total Annexin expression. All expressed Annexins translocated to the cell surface upon apoptosis induction in all cell lines. Human expression data indicate a correlation between immune infiltration and overall Annexin expression in malignant compared to healthy tissue.

This study is the first comprehensive analysis of expression, distribution and presentation of Annexins in cancer.

The online version contains supplementary material available at 10.1186/s12885-022-10075-8.

• Annexins
• Apoptotic cells
• Immunosuppression
• Peripheral tolerance
• Tumour microenvironment

To fulfil its orchestration of immune cell trafficking, a network of chemokines and receptors developed that capitalizes on specificity, redundancy, and functional selectivity. The discovery of heteromeric interactions in the chemokine interactome has expanded the complexity within this network. Moreover, some inflammatory mediators, not structurally linked to classical chemokines, bind to chemokine receptors and behave as atypical chemokines (ACKs). We identified macrophage migration inhibitory factor (MIF) as an ACK that binds to chemokine receptors CXCR2 and CXCR4 to promote atherogenic leukocyte recruitment. Here, we hypothesized that chemokine–chemokine interactions extend to ACKs and that MIF forms heterocomplexes with classical chemokines. We tested this hypothesis by using an unbiased chemokine protein array. Platelet chemokine CXCL4L1 (but not its variant CXCL4 or the CXCR2/CXCR4 ligands CXCL8 or CXCL12) was identified as a candidate interactor. MIF/CXCL4L1 complexation was verified by co-immunoprecipitation, surface plasmon-resonance analysis, and microscale thermophoresis, also establishing high-affinity binding. We next determined whether heterocomplex formation modulates inflammatory/atherogenic activities of MIF. Complex formation was observed to inhibit MIF-elicited T-cell chemotaxis as assessed by transwell migration assay and in a 3D-matrix-based live cell-imaging set-up. Heterocomplexation also blocked MIF-triggered migration of microglia in cortical cultures in situ, as well as MIF-mediated monocyte adhesion on aortic endothelial cell monolayers under flow stress conditions. Of note, CXCL4L1 blocked binding of Alexa-MIF to a soluble surrogate of CXCR4 and co-incubation with CXCL4L1 attenuated MIF responses in HEK293-CXCR4 transfectants, indicating that complex formation interferes with MIF/CXCR4 pathways. Because MIF and CXCL4L1 are platelet-derived products, we finally tested their role in platelet activation. Multi-photon microscopy, FLIM-FRET, and proximity-ligation assay visualized heterocomplexes in platelet aggregates and in clinical human thrombus sections obtained from peripheral artery disease (PAD) in patients undergoing thrombectomy. Moreover, heterocomplexes inhibited MIF-stimulated thrombus formation under flow and skewed the lamellipodia phenotype of adhering platelets. Our study establishes a novel molecular interaction that adds to the complexity of the chemokine interactome and chemokine/receptor-network. MIF/CXCL4L1, or more generally, ACK/CXC-motif chemokine heterocomplexes may be target structures that can be exploited to modulate inflammation and thrombosis.

• Heterodimer
• chemotaxis
• leukocytes
• platelets
• protein-protein interaction
• thrombosis

• Cell Differentiation/genetics
• Cell Line
• Humans
• Monocytes/metabolism
• Neutrophils
• Transcriptome

• Semmelweis Egyetem
• Szint+ Programme
• Foundation for the Hungarian Peptide and Protein Research
• Nemzeti Kutatási Fejlesztési és Innovációs Hivatal
• European Regional Development Fund

• Dhvar4
• MonoMac-6
• Transwell
• cell penetrating peptides
• isoniazid
• spheroid
• tuberculosis

• Animals
• Antimicrobial Peptides/administration & dosage
• Antimicrobial Peptides/chemistry
• Antitubercular Agents/administration & dosage
• Antitubercular Agents/chemistry
• Biological Assay/methods
• Bronchi
• Cell Line
• Cell-Penetrating Peptides/administration & dosage
• Cell-Penetrating Peptides/chemistry
• Endocytosis
• Female
• Humans
• Isoniazid/administration & dosage
• Isoniazid/chemistry
• Mice, Inbred BALB C
• Monocytes/microbiology
• Mycobacterium tuberculosis/drug effects
• Mycobacterium tuberculosis/growth & development
• Reproducibility of Results
• Spheroids, Cellular
• Tuberculosis/drug therapy
• Mice

• Rituximab
• antibody-dependent phagocytosis (ADP)
• complement-dependent cytotoxicity (CDC)
• human 3D tumor-immune model
• isotypes

• 2,3-dihydrobenzofuran
• absorption spectrometry
• colony-forming units
• coumaran
• dynamic light scattering
• flow cytometry
• monocomponent liposome
• pH-sensitive stealth liposome

• Antitubercular Agents/chemistry
• Antitubercular Agents/pharmacology
• Cell Proliferation
• Cells, Cultured
• Drug Compounding/methods
• Drug Delivery Systems
• Drug Design
• Humans
• Liposomes/administration & dosage
• Liposomes/chemistry
• Monocytes/drug effects
• Mycobacterium tuberculosis/drug effects
• Tuberculosis/drug therapy
• Tuberculosis/microbiology

• NKFIH-1157-8/2019-DT Higher Education Institutional Excellence Program of the Ministry for Innovation and Technology in Hungary, within the framework of the Therapeutic Development thematic program of Semmelweis University: 2019, ELTE Institutional Excellence Program (NKFIH-1

In the bone marrow (BM) hematopoietic niche, the oxygen tension is usually very low. Such condition affects stem and progenitor cell proliferation and differentiation and, at cellular level regulates hematopoietic growth factors, chemokines and adhesion molecules expression. In turn, these molecules affect the proliferation and maturation of other cellular components of the niche. Due to the complexity of the system we started the in vitro investigations of the IL-6, IL-8, TNFα cytokines expression and the vascular endothelial growth factor (VEGF), considered key mediators of the hematopoietic niche, in human macrophages and macrophage cell line. Since in the niche the oxygen availability is mediated by red blood cells (RBCs), we have influenced the anoxic cell cultures by the administration of oxygenated or deoxygenated RBCs (deoxy RBCs). The results reported in this brief paper show that the presence of RBCs up-regulates IL-8 mRNA while IL-6 and VEGF mRNA expression appears down-regulated. This does not occur when deoxy RBCs are used. Moreover, it appears that the administration of RBCs leads to an increase of TNFα expression levels in MonoMac 6 (MM6). Interestingly, the modulation of these factors likely occurs in a hypoxia-inducible factor-1α (HIF-1α) independent manner. Considering the role of oxygen in the hematopoietic niche further studies should explore these preliminary observations in more details.

• cytokine expression modulation
• hypoxia
• macrophages
• pO2 variation
• red blood cells

This study aimed to examine the effects of tumour necrosis factor-alpha (TNF-α) on osteoblasts in metal wear-induced bone loss.

TNF-α immunoexpression was examined in periprosthetic tissues of patients with failed metal-on-metal hip arthroplasties and also in myeloid MM6 cells after treatment with cobalt ions. Viability and function of human osteoblast-like SaOs-2 cells treated with recombinant TNF-α were studied by immunofluorescence, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assay, western blotting, and enzyme-linked immunosorbent assay (ELISA).

Macrophages, lymphocytes, and endothelial cells displayed strong TNF-α immunoexpression in periprosthetic tissues containing metal wear debris. Colocalization of TNF-α with the macrophage marker CD68 and the pan-T cell marker CD3 confirmed TNF-α expression in these cells. Cobalt-treated MM6 cells secreted more TNF-α than control cells, reflecting the role of metal wear products in activating the TNF-α pathway in the myeloid cells. While TNF-α did not alter the immunoexpression of the TNF-receptor 1 (TNF-R1) in SaOs-2 cells, it increased the release of the soluble TNF-receptor 1 (sTNF-R1). There was also evidence for TNF-α-induced apoptosis. TNF-α further elicited the expression of the endoplasmic reticulum stress markers inositol-requiring enzyme (IRE)-1α, binding-immunoglobulin protein (BiP), and endoplasmic oxidoreductin1 (Ero1)-Lα. In addition, TNF-α decreased pro-collagen I α 1 secretion without diminishing its synthesis. TNF-α also induced an inflammatory response in SaOs-2 cells, as evidenced by the release of reactive oxygen and nitrogen species and the proinflammatory cytokine vascular endothelial growth factor.

The results suggest a novel osteoblastic mechanism, which could be mediated by TNF-α and may be involved in metal wear debris-induced periprosthetic bone loss.

Cite this article: Bone Joint Res 2020;9(11):827–839.

• Bone loss
• Endoplasmic reticulum stress
• Implant loosening
• Osteoblast
• Tumour necrosis factor-alpha

• Dectin-1
• NOX-2
• SYK
• annexin (A1, A5, and A13)
• apoptotic cells
• autoimmunity
• biased agonism
• dendritic cells
• peripheral immune tolerance
• reactive oxygen species

• Bone Marrow-derived Dendritic Cells (BMDCs)
• Jurkat T cells
• Mono Mac 6 (MM6) cells
• NADPH-oxidase 2 (NOX-2)
• Reactive Oxygen Species (ROS)

• STING
• adjuvant
• cytokine
• cytosolic DNA sensing
• interferon

• Alleles
• Animals
• Drug Discovery
• Humans
• Immunity, Innate/drug effects
• Immunity, Innate/immunology
• Immunologic Factors/pharmacology
• Membrane Proteins/agonists
• Membrane Proteins/genetics
• Membrane Proteins/immunology
• Mice

• R21 CA256295 NCI NIH HHS
• R01 AI143660 NIAID NIH HHS
• U19 AI142759 NIAID NIH HHS
• HHSN272201400055C NIAID NIH HHS
• U19 AI109680 NIAID NIH HHS

Several factors can contribute to neuroinflammatory disorders, such as cytokine and chemokines that are produced and released from peripherally derived immune cells or from locally activated cells such as microglia and perivascular macrophages in the brain. The primary function of these cells is to clear inflammation; however, following inflammation, circulating monocytes are recruited to the central nervous system (CNS). Monocyte-derived macrophages in the CNS play pivotal roles in mediating neuroinflammatory responses. Macrophages are heterogeneous both in normal and in pathological conditions due to their plasticity, and they are classified in two main subsets, classically activated (M1) or alternatively activated (M2). There is accumulating evidence suggesting that extracellular vesicles (EVs) released from activated immune cells may play crucial roles in mediating inflammation. However, a possible role of EVs released from immune cells such as M1 and M2 macrophages on neuronal functions in the brain is not known. In order to investigate the molecular and cellular impacts of macrophages and EVs released from macrophage subtypes on neuronal functions, we used a recently established in vitro M1 and M2 macrophage culture model and isolated and characterized EVs from these macrophage subtypes, treated primary neurons with M1 or M2 EVs, and analyzed the extracellular action potentials of neurons with microelectrode array studies (MEA). Our results introduce evidence on the interfering role of inflammatory EVs released from macrophages in interneuronal signal transmission processes, with implications in the pathogenesis of neuroinflammatory diseases induced by a variety of inflammatory insults.

• CD163
• M1and M2 macrophages
• action potential
• exosomes
• neuroinflammation

• P51 OD011104 NIH HHS
• P30MH092177 NIH HHS

The aims of the present study were: (a) to determine the mechanism of action of taurolidine against bacterial species associated with periodontal disease, and (b) to evaluate the potential development of resistance against taurolidine as compared with minocycline. After visualizing the mode of action of taurolidine by transmission electron micrographs, the interaction with most important virulence factors (lipopolysaccharide (LPS), Porphyromonas gingivalis gingipains, Aggregatibacter actinomycetemcomitans leukotoxin), was analyzed. Then, 14 clinical isolates from subgingival biofilm samples were transferred on agar plates containing subinhibitory concentrations of taurolidine or minocycline up to 50 passages. Before and after each 10 passages, minimal inhibitory concentrations (MICs) were determined. Increasing MICs were screened for efflux mechanism. Taurolidine inhibited in a concentration-dependent manner the activities of LPS and of the arginine-specific gingipains; however, an effect on A. actinomycetemcomitans leukotoxin was not detected. One P. gingivalis strain developed a resistance against taurolidine, which was probably linked with efflux mechanisms. An increase of MIC values of minocycline occurred in five of the 14 included strains after exposure to subinhibitory concentrations of the antibiotic. The present results indicate that: (a) taurolidine interacts with LPS and gingipains, and (b) development of resistance seems to be a rare event when using taurolidine.

• development of resistance
• mechanisms of action
• minocycline
• periodontal pathogens
• taurolidine

• Aggregation
• antimicrobial peptides
• food colors
• membrane biophysics
• molecular mechanism

• Inflammation
• Leukotrienes
• Mono Mac 1
• Reporter gene assays
• TGF-β
• THP-1

• Arachidonate 5-Lipoxygenase/genetics
• Arachidonate 5-Lipoxygenase/metabolism
• Cell Differentiation/drug effects
• Cell Line
• Drug Synergism
• Gene Expression Regulation, Enzymologic/drug effects
• Gene Expression Regulation, Neoplastic/drug effects
• Humans
• Lipopolysaccharides/pharmacology
• Promoter Regions, Genetic/drug effects
• THP-1 Cells
• Transforming Growth Factor beta1/pharmacology

• CIHR

Genetically modified T cells expressing chimeric antigen receptors (CARs) so far have mostly failed in the treatment of solid tumors owing to a number of limitations, including an immunosuppressive tumor microenvironment and insufficient CAR T cell activation and persistence. Next-generation approaches using CAR T cells that secrete transgenic immunomodulatory cytokines upon CAR signaling, known as TRUCKs (“T cells redirected for universal cytokine-mediated killing”), are currently being explored. As TRUCKs were engineered by the transduction of T cells with two separate vectors, we developed a lentiviral modular “all-in-one” vector system that combines constitutive CAR expression and inducible nuclear factor of activated T cells (NFAT)-driven transgene expression for more efficient production of TRUCKs. Activation of the G_D2-specific CAR via GD2⁺ target cells induced NFAT promoter-driven cytokine release in primary human T cells, and indicated a tight linkage of CAR-specific activation and transgene expression that was further improved by a modified NFATsyn promoter. As proof-of-concept, we showed that T cells containing the “all-in-one” vector system secrete the immunomodulatory cytokines interleukin (IL)12 or IL18 upon co-cultivation with primary human GD2⁺ tumor cells, resulting in enhanced effector cell properties and increased monocyte recruitment. This highlights the potential of our system to simplify application of TRUCK-modified T cells in solid tumor therapy.

• GD2CAR
• IL12
• IL18
• NFAT
• TRUCK
• glioblastoma
• inducible cytokines
• “all-in-one” lentiviral vector

Epitopes from different proteins expressed by Mycobacterium tuberculosis (Rv1886c, Rv0341, Rv3873) were selected based on previously reported antigenic properties. Relatively short linear T-cell epitope peptides generally have unordered structure, limited immunogenicity, and low in vivo stability. Therefore, they rely on proper formulation and on the addition of adjuvants. Here we report a convenient synthetic route to induce a more potent immune response by the formation of a trivalent conjugate in spatial arrangement. Chemical and structural characterization of the vaccine conjugates was followed by the study of cellular uptake and localization. Immune response was assayed by the measurement of splenocyte proliferation and cytokine production, while vaccine efficacy was studied in a murine model of tuberculosis. The conjugate showed higher tendency to fold and increased internalization rate into professional antigen presenting cells compared to free epitopes. Cellular uptake was further improved by the incorporation of a palmitoyl group to the conjugate and the resulted pal-A(P)I derivative possessed an internalization rate 10 times higher than the free epitope peptides. Vaccination of CB6F1 mice with free peptides resulted in low T-cell response. In contrast, significantly higher T-cell proliferation with prominent expression of IFN-γ, IL-2, and IL-10 cytokines was measured for the palmitoylated conjugate. Furthermore, the pal-A(P)I conjugate showed relevant vaccine efficacy against Mycobacterium tuberculosis infection.

• Mycobacterium tuberculosis
• T-cell epitope
• maleimide conjugation
• peptide-based vaccines
• tuftsin

• IR spectroscopy
• antimicrobial peptides
• circular dichroism
• folding
• suramin

• Anti-Infective Agents/chemistry
• Anti-Infective Agents/pharmacology
• Antimicrobial Cationic Peptides/chemistry
• Antimicrobial Cationic Peptides/pharmacology
• Cells, Cultured
• Circular Dichroism/methods
• Escherichia coli
• Humans
• Lipid Bilayers/chemistry
• Protein Structure, Secondary
• Suramin/chemistry
• Suramin/pharmacology

Lentiviruses have evolved to acquire an auxiliary protein Vpx to counteract the intrinsic host restriction factor SAMHD1. Although Vpx is phosphorylated, it remains unclear whether such phosphorylation indeed regulates its activity toward SAMHD1. Here we identify the PIM family of serine/threonine protein kinases as the factors responsible for the phosphorylation of Vpx and the promotion of Vpx-mediated SAMHD1 counteraction. Integrated proteomics and subsequent functional analysis reveal that PIM family kinases, PIM1 and PIM3, phosphorylate HIV-2 Vpx at Ser13 and stabilize the interaction of Vpx with SAMHD1 thereby promoting ubiquitin-mediated proteolysis of SAMHD1. Inhibition of the PIM kinases promotes the antiviral activity of SAMHD1, ultimately reducing viral replication. Our results highlight a new mode of virus–host cell interaction in which host PIM kinases facilitate promotion of viral infectivity by counteracting the host antiviral system, and suggest a novel therapeutic strategy involving restoration of SAMHD1-mediated antiviral response.

The accessory lentiviral protein X (Vpx) of the SIV_smm/mac and HIV-2 lineage targets the host-restriction factor SAMHD1 for proteasomal degradation. Here, the authors show that host PIM kinase-mediated phosphorylation of Vpx stabilizes its interaction with SAMHD1, suggesting PIM as potential antiviral targets.

• Diabetes mellitus type 2
• Endothelial cells
• Exosomes
• Hyperglycemia
• ICAM-1
• Monocytes

Zinc finger protein 580 (ZNF580) was reported to modulate angiogenesis, endothelial homeostasis and blood pressure control. ZNF580 regulated genes include VEGF-A and IL-8. However, it is unknown if ZNF580 could play a role during inflammation. The aim of this study was to find out if ZNF580 affects the expression of IL-6, if it occurs in monocytic cells and responds to inflammatory mediators.

Overexpression of ZNF580 reduced LPS-induced promotor activity of IL-6. Consistently, overexpression of ZNF580 reduced by half the LPS-induced expression of IL-6. ZNF580 was strongly expressed in the nucleus of MonoMac6, a human monocytic cell line. LPS-stimulated IL-6 secretion increased when ZNF580 was suppressed with siRNA. After stimulation of MonoMac6 with LPS for 24 h, ZNF580 negatively correlated with the amount of secreted IL-6. In response to LPS, ZNF580 was increased within the first 8 h, followed by a marked decrease after 16 h. This decrease coincided with sustained IL-6 production.

This study demonstrated that ZNF580 inhibits LPS-induced expression of IL-6. ZNF580 was highly expressed in monocytic cells and therefore may contribute to the modulation of its IL-6 production, at least in response to LPS. This suggests cooperation between ZNF580 and NFκB, which could play a role during sepsis.

• Interleukin 6
• LPS
• Monocytes
• Sepsis
• ZNF580

• ROS
• arthroplasty
• cobalt particles + ions
• immune cells
• superoxide

• Cell-penetrating peptides
• Cellular uptake
• Fluorescent labelling
• Lipid monolayer
• Membrane affinity
• Penetration

• cAMP
• cathelicidin
• eicosanoids
• innate immunity
• vitamin D3

Pentraxins are a family of highly conserved secreted proteins that regulate the innate immune system, including monocytes and macrophages. C-reactive protein (CRP) is a plasma protein whose levels can rise to 1000 μg/ml from the normal <3 μg/ ml during inflammation.

We find that CRP inhibits proliferation of the human myeloid leukemia cell line Mono Mac 6 with an IC50 of 75 μg/ ml by inducing apoptosis of these cells. The related proteins serum amyloid P (SAP) and pentraxin 3 (PTX3) do not inhibit Mono Mac 6 proliferation. CRP has no significant effect on the proliferation of other leukemia cell lines such as HL-60, Mono Mac 1, K562, U937, or THP-1, or the survival of normal peripheral blood cells. The effect of CRP appears to be dependent on the CRP receptor FcγRI, and is negatively regulated by a phosphatidylinositol −3-kinase pathway.

These data reveal differential signaling by pentraxins on immune cells, and suggest that CRP can regulate the proliferation of some myeloid leukemia cells.

• Apoptosis
• C reactive protein
• Leukemia
• Pentraxin

• 4-(Trifluoromethyl)benzohydrazide
• Antibacterial activity
• Antifungal activity
• Cytostasis
• Cytotoxicity
• Hydrazone
• Mycobacterium tuberculosis
• Nontuberculous mycobacteria

• Animals
• Anti-Infective Agents/chemical synthesis
• Anti-Infective Agents/pharmacology
• Anti-Infective Agents/toxicity
• Candida glabrata/drug effects
• Cell Line
• Cell Survival/drug effects
• Hep G2 Cells
• Humans
• Hydrazones/chemistry
• Hydrazones/pharmacology
• Hydrazones/toxicity
• Mice
• Microbial Sensitivity Tests
• Mycobacterium avium Complex/drug effects
• Mycobacterium kansasii/drug effects
• Mycobacterium tuberculosis/drug effects