Role Of Macrophage Colony-stimulating Factor Research Articles

The Role of Macrophage Dynamics in Atherosclerosis Analyzed Using a Petri Net-Based Model

Atherosclerosis, a chronic inflammatory and oxidative stress-mediated disease impacting the arterial system, stands as a primary cause of morbidity and mortality worldwide. The complexity of this disease, driven by numerous factors, requires a thorough investigation of its underlying mechanisms. In our study, we explore the complex interplay between cholesterol homeostasis, macrophage dynamics, and atherosclerosis development using a Petri net-based model anchored in credible, peer-reviewed biological and medical research. Our findings underscore the significant role of macrophage colony-stimulating factor (M-CSF) inhibition in reducing atherosclerotic plaque formation by modulating inflammatory responses and lipid accumulation. Furthermore, our model highlights the therapeutic potential of targeting the C-X-C motif ligand 12 (CXCL12)/ C-X-C motif chemokine receptor type 4 (CXCR4) pathway to hinder hematopoietic stem and progenitor cells’ (HSPCs’) mobilization and plaque development. Based on the results obtained, which are in agreement with current studies, additional strategies are also proposed, such as decreasing M1 macrophage polarization for therapeutic gains, opening the door to future research and novel treatment approaches.

Macrophage colony-stimulating factor and its role in the tumor microenvironment: novel therapeutic avenues and mechanistic insights.

The tumor microenvironment is a complex ecosystem where various cellular and molecular interactions shape the course of cancer progression. Macrophage colony-stimulating factor (M-CSF) plays a pivotal role in this context. This study delves into the biological properties and functions of M-CSF in regulating tumor-associated macrophages (TAMs) and its role in modulating host immune responses. Through the specific binding to its receptor colony-stimulating factor 1 receptor (CSF-1R), M-CSF orchestrates a cascade of downstream signaling pathways to modulate macrophage activation, polarization, and proliferation. Furthermore, M-CSF extends its influence to other immune cell populations, including dendritic cells. Notably, the heightened expression of M-CSF within the tumor microenvironment is often associated with dismal patient prognoses. Therefore, a comprehensive investigation into the roles of M-CSF in tumor growth advances our comprehension of tumor development mechanisms and unveils promising novel strategies and approaches for cancer treatment.

Role of Macrophage Colony-Stimulating Factor for Staphylococcal Infection in the Oral Cavity.

There are few valid indicators of oral infection owing to the complexity of pathogenic factors in oral diseases. Salivary markers are very useful for scrutinizing the symptoms of disease. To provide a reliable and useful predictive indicator of infection for opportunistic pathogens in individuals with compromised immune systems, such as those with periodontal diseases and Human Immunodeficiency Virus (HIV), this study examines opportunistic pathogens such as C. albicans and staphylococci and macrophage colony-stimulating factor (M-CSF) and CA125/MUC16 in saliva. The aim was to explore the correlations investigated among these factors. Samples were divided into two groups (based on patient sex, the absence and presence of dentures in elderly, or HIV-positive patients and healthy subjects), and the correlation was analyzed in two groups of elderly patients with periodontal disease (64.5 ± 11.2 years old) and HIV-infected patients (41.9 ± 8.4 years old). Healthy subjects (33.8 ± 9.1 years old) were also analyzed as a control. Levels of C. albicans, staphylococci, and M-CSF, which is an immunological factor for the differentiation of macrophage, and CA125/MUC16, which provides a protective lubricating barrier against infection, were investigated. A significant and positive correlation between the levels of M-CSF and staphylococci was found in elderly individuals and HIV-positive patients treated with antiretroviral therapy. A significant and positive correlation between the levels of M-CSF and CD125/MUC16 was also found in both patients. These correlations were enhanced in both patients as compared with healthy subjects. Salivary M-CSF might be useful as a new indicator of opportunistic infection caused by staphylococci and a defense against infection in immunocompromised hosts.

The Potential Clinical Application of Induced Tolerogenic Macrophages.

The Potential Clinical Application of Induced Tolerogenic Macrophages.

Augmenting MNK1/2 activation by c-FMS proteolysis promotes osteoclastogenesis and arthritic bone erosion

Osteoclasts are bone-resorbing cells that play an essential role in homeostatic bone remodeling and pathological bone erosion. Macrophage colony stimulating factor (M-CSF) is abundant in rheumatoid arthritis (RA). However, the role of M-CSF in arthritic bone erosion is not completely understood. Here, we show that M-CSF can promote osteoclastogenesis by triggering the proteolysis of c-FMS, a receptor for M-CSF, leading to the generation of FMS intracellular domain (FICD) fragments. Increased levels of FICD fragments positively regulated osteoclastogenesis but had no effect on inflammatory responses. Moreover, myeloid cell-specific FICD expression in mice resulted in significantly increased osteoclast-mediated bone resorption in an inflammatory arthritis model. The FICD formed a complex with DAP5, and the FICD/DAP5 axis promoted osteoclast differentiation by activating the MNK1/2/EIF4E pathway and enhancing NFATc1 protein expression. Moreover, targeting the MNK1/2 pathway diminished arthritic bone erosion. These results identified a novel role of c-FMS proteolysis in osteoclastogenesis and the pathogenesis of arthritic bone erosion.

Roles of Macrophage Colony Stimulating Factor in White and Brown Adipocytes

Macrophage colony stimulating factor (M-CSF), commonly known as CSF1, is a cytokine produced by osteoblast cells, and is well known for its important role in differentiation of osteoclasts and white adipocyte hyperplasia. However, the role of M-CSF in lipid metabolic activity is lacking insight. In the current study, we explore unidentified actions of M-CSF in adipocytes. Levels of M-CSF were determined for white and brown adipose tissues and cells, and the expression levels of the important protein markers in lipid metabolism were evaluated through immunoblot analysis, subsequent to blocking M-CSF in fat cells by silencing its receptor Csf1r. Interestingly, we observed presence of M-CSF in brown fat cells. In addition, the lack of M-CSF in HIB1B cells attenuated the expressions of protein markers responsible for lipid metabolism in the brown adipocytes. Further, deficiency of M-CSF resulted in decreased adipogenesis along with reduced expression of lipogenic markers for both white and brown adipocytes. Moreover, lipid metabolism was balanced by M-CSF via the PPARγ-mediated LPL activity in white adipocytes. Taken together, the results from this study indicate that MCSF is an important regulatory protein in both white and brown adipocytes.

Association of plasma macrophage colony-stimulating factor with cardiovascular morbidity and all-cause mortality in chronic hemodialysis patients

BackgroundCardiovascular disease (CVD) events are the main cause of death in long-term hemodialysis (HD) patients. Macrophage colony- stimulating factor (M-CSF) is actively involved in the formation of atherosclerosis and causes plaque instability, thrombosis and the development of acute coronary syndromes. However, little information is available on the role of M-CSF in HD patients. We aimed to investigate the association between plasma M-CSF levels and CVD events as well as all-cause mortality in patients undergoing long-term HD.MethodsFifty two HD patients and 8 healthy controls were recruited in this study. HD patients were followed up from September 2014 to May 2017. The primary end point was CVD event, the secondary outcome was death from any cause. Patients were divided into two groups with low and high M-CSF levels based on the optimal cut-off value determined by the ROC curve. Cox regression analyses were used to assess the predictive value of plasma M-CSF for CVD events and all-cause mortality in HD patients. We tested the levels of plasma M-CSF and other inflammatory cytokines in surviving HD patients using ELISA or CBA kit.ResultsThe average plasma level of M-CSF in 52 patients was approximately twice that of healthy controls (992.4 vs. 427.2 pg/mL; p < 0.05). During 32 months of follow-up, 26 patients (50.0%) had at least one CVD event and 8 patients (15.4%) died. The mean plasma M-CSF concentration increased in survivors after follow-up compared to that detected at baseline (1277.8 ± 693.3 vs. 997.2 ± 417.4 pg/mL; p < 0.05). Multivariate Cox regression analysis showed that plasma M-CSF is an independent risk factor for CVD events in HD patients (p < 0.05). In the Cox regression model after adjusting for gender and age, high M-CSF levels were related to an increased risk of all-cause death (p < 0.05). We also found that M-CSF levels were positively correlated with IL-6 and IL-18 levels (both p < 0.05), which are the major pathogentic cytokines that contribute to HD-related CVD events.ConclusionM-CSF is a prognostic factor for CVD events and all-cause mortality in HD patients.

MCSF orchestrates branching morphogenesis in developing submandibular gland tissue

The importance of macrophages in tissue development and regeneration has been strongly emphasized. However, the specific roles of macrophage colony-stimulating factor (MCSF), the key regulator of macrophage differentiation, in glandular tissue development have been unexplored. Here, we disclose new macrophage-independent roles of MCSF in tissue development. We initially found that MCSF is markedly upregulated at embryonic day (E)13.5, at a stage preceding the colonization of macrophages (at E15.5), in mouse submandibular gland (SMG) tissue. Surprisingly, MCSF-induced branching morphogenesis was based on a direct effect on epithelial cells, as well as indirectly, by modulating the expression of major growth factors of SMG growth, FGF7 and FGF10, via the phosphoinositide 3-kinase (PI3K) pathway. Additionally, given the importance of neurons in SMG organogenesis, we found that MCSF-induced SMG growth was associated with regulation of neurturin expression and neuronal network development during early SMG development in an in vitro organogenesis model as well as in vivo These results indicate that MCSF plays pleiotropic roles and is an important regulator of early SMG morphogenesis.

Molecular mechanism and functional role of macrophage colony‑stimulating factor in follicular granulosa cells.

Our previous demonstrated that macrophage colony‑stimulating factor (M‑CSF) stimulated the production of estradiol (E2) and progesterone (P) in luteinized granulosa cells (GCs), and that its secretion may be regulated by follicle‑stimulating hormone (FSH). The present study aimed to examine the effect of M‑CSF alone or with Letrozole treatment on the function of non‑luteinizing granulosa cells, using the COV434cell line, and its interaction with FSH. Human luteinized granulosa cells (LGC) were isolated from the follicular fluid of superovulated infertile patients (average age, 30.8±2.1years) undergoing an intracytoplasmic sperm injection. The LGC were cultured with various concentrations of recombinant human macrophage colony stimulating factor (rhM‑CSF; 0, 10, 25, 50 or 100ng/ml), rhM‑CSF+Letrozole (10‑6mol/l), rhFSH (0, 10, 25, 50 or 100IU/ml), or rhFSH+Letrozole (10‑6 mol/l). E2 concentrations in the media were measured using ELISA. The expression levels of the FSH receptor and the M‑CSF receptor were detected via reverse transcription‑quantitative polymerase chain reaction. Following COV434cell treatment with M‑CSF, cell proliferation was quantified using the MTS assay and protein expression was detected by western blotting. It was demonstrated that M‑CSF and FSH stimulated the production of E2. The production of FSH receptors was enhanced by rhM‑CSF or rhM‑CSF+Letrozole invitro in a dose‑dependent manner. It was observed that rhFSH promoted the expression of the M‑CSF receptor, at a certain concentration. Proliferation of COV434cells increased in a dose‑dependent manner following treatment with RhM‑CSF. Furthermore, M‑CSF induced the phosphorylation of c‑Jun N‑terminal kinase (JNK) and p38; however, the level of E2 in the medium was not altered when the cells were pretreated with the JNK inhibitor SP600125 or the p38 inhibitor SB203580. The present study suggested that M‑CSF may be important in regulating the response of GCs to gonadotropin and may have a promotive effect in the early phase of follicular development. The biological effects of M‑CSF may partially be attributed to activation of the JNK and p38 signaling pathways. M‑CSF may represent a novel follicular development regulator agent in the future.

MCSF orchestrates branching morphogenesis in developing submandibular gland tissue

The importance of macrophages in tissue development and regeneration has been strongly emphasized. However, the specific roles of macrophage colony-stimulating factor (MCSF), the key regulator of macrophage differentiation, in glandular tissue development have been unexplored. Here, we disclose new macrophage-independent roles of MCSF in tissue development. We initially found that MCSF is markedly upregulated at embryonic day (E)13.5, at a stage preceding the colonization of macrophages (at E15.5), in mouse submandibular gland (SMG) tissue. Surprisingly, MCSF-induced branching morphogenesis was based on a direct effect on epithelial cells, as well as indirectly, by modulating the expression of major growth factors of SMG growth, FGF7 and FGF10, via the phosphoinositide 3-kinase (PI3K) pathway. Additionally, given the importance of neurons in SMG organogenesis, we found that MCSF-induced SMG growth was associated with regulation of neurturin expression and neuronal network development during early SMG development in an in vitro organogenesis model as well as in vivo These results indicate that MCSF plays pleiotropic roles and is an important regulator of early SMG morphogenesis.

Role of macrophage colony-stimulating factor (M-CSF) in human granulosa cells

Macrophage colony-stimulating factor (M-CSF) has been proved to have a positive role in the follicular development. We investigated its effect on human granulosa cells and found that M-CSF could stimulate the production of E2. The production of FSH receptors was enhanced by M-CSF in vitro in a dose-dependent manner with or without the addition of tamoxifen (p <0.05). Correspondingly, FSH was also able to coordinate the expression of M-CSF and its receptor (p <0.05). That maybe important to maintain the level of Nppc and the meiotic arrest of the oocyte. The protein p-JAK2 and p-STAT3 in JAK/STAT-signaling pathway elevated after the influence of M-CSF (p < 0.05). These results suggest that M-CSF has a role in regulating the response of granulosa cells to gonadotropins. Its function is associated with JAK/STAT-signaling pathway.

Role of macrophage colony-stimulating factor in the development of neointimal thickening following arterial injury.

Evidence suggests that macrophage colony-stimulating factor (M-CSF) participates critically in atherosclerosis; little is known about the role of M-CSF in the development of neointimal hyperplasia following mechanical vascular injury. We examined the expression of M-CSF and its receptor, c-fms, in rodent and rabbit models of arterial injury. Injured rat carotid arteries expressed 3- to 10-fold higher levels of M-CSF and c-fms mRNA and protein following balloon injury as compared to uninjured arteries. In the rabbit, M-CSF protein expression was greatest in neointimal smooth muscle cells (SMCs) postinjury, with some expression in medial SMCs. M-CSF-positive SMCs exhibited markers of proliferation. At 30days postinjury, neointimal SMCs in the adjacent healed area near the border between injured and uninjured zone lost both proliferative activity and overexpression of M-CSF. The presence of induced M-CSF and c-fms expression correlated with the initiation of SMCs proliferation. M-CSF stimulated incorporation of [(3)H] thymidine in human aortic smooth muscle cells in a concentration-dependent manner. Serum-free conditioned medium from aortic SMCs also promoted DNA synthesis, and this effect was blocked by M-CSF specific antibody. To test further the role of M-CSF in vivo, we induced arterial injury by placing a periadventitial collar around the carotid arteries in compound mutant mice lacking apolipoprotein apoE (apoE(-/-)) and M-CSF. Loss of M-CSF abolished the neointimal hyperplastic response to arterial injury in apoE(-/-) mice. Local delivery of M-CSF to the injured artery restored neointimal proliferation, suggesting a critical role of M-CSF for the development of neointimal thickening following arterial injury.

Macrophage colony-stimulating factor expressed in non-cancer tissues provides predictive powers for recurrence in hepatocellular carcinoma.

AIMTo investigate the role of macrophage colony-stimulating factor (M-CSF) in patients with hepatocellular carcinoma (HCC) after surgery.METHODSExpression of M-CSF, distribution of M2 macrophages (MΦs), and angiogenesis were assessed in the liver, including tumors and peritumoral liver tissues. The prognostic power of these factors was assessed. Mouse isolated hepatic MΦs or monocytes were cultured with media containing M-CSF. The concentration of vascular endothelial growth factor (VEGF) in media was assessed. Furthermore, the role of the M-CSF-matured hepatic MΦs on proliferation of the vascular endothelial cell (VEC) was investigated.RESULTSA strong correlation between the expressions of M-CSF and CD163 was observed in the peritumoral area. Also, groups with high density of M-CSF, CD163 or CD31 showed a significantly shorter time to recurrence (TTR) than low density groups. Multivariate analysis revealed the expression of M-CSF or hepatic M2MΦs in the peritumoral area as the most crucial factor responsible for shorter TTR. Moreover, the expression of M-CSF and hepatic M2MΦs in the peritumoral area had better predictable power of overall survival. Values of VEGF in culture media were significantly greater in the hepatic MΦs compared with the monocytes. Proliferation of the VEC was greatest in the cells co-cultured with hepatic MΦs when M-CSF was present in media.CONCLUSIONM-CSF increases hepatocarcinogenesis, most likely by enhancing an angiogenic factor derived from hepatic MΦ and could be a useful target for therapy against HCC.

M-CSF and GM-CSF Receptor Signaling Differentially Regulate Monocyte Maturation and Macrophage Polarization in the Tumor Microenvironment.

Tumors contain a heterogeneous myeloid fraction comprised of discrete MHC-II(hi) and MHC-II(lo) tumor-associated macrophage (TAM) subpopulations that originate from Ly6C(hi) monocytes. However, the mechanisms regulating the abundance and phenotype of distinct TAM subsets remain unknown. Here, we investigated the role of macrophage colony-stimulating factor (M-CSF) in TAM differentiation and polarization in different mouse tumor models. We demonstrate that treatment of tumor-bearing mice with a blocking anti-M-CSFR monoclonal antibody resulted in a reduction of mature TAMs due to impaired recruitment, extravasation, proliferation, and maturation of their Ly6C(hi) monocytic precursors. M-CSFR signaling blockade shifted the MHC-II(lo)/MHC-II(hi) TAM balance in favor of the latter as observed by the preferential differentiation of Ly6C(hi) monocytes into MHC-II(hi) TAMs. In addition, the genetic and functional signatures of MHC-II(lo) TAMs were downregulated upon M-CSFR blockade, indicating that M-CSFR signaling shapes the MHC-II(lo) TAM phenotype. Conversely, granulocyte macrophage (GM)-CSFR had no effect on the mononuclear tumor infiltrate or relative abundance of TAM subsets. However, GM-CSFR signaling played an important role in fine-tuning the MHC-II(hi) phenotype. Overall, our data uncover the multifaceted and opposing roles of M-CSFR and GM-CSFR signaling in governing the phenotype of macrophage subsets in tumors, and provide new insight into the mechanism of action underlying M-CSFR blockade.

Macrophage colony-stimulating factor (M-CSF) in first trimester maternal serum: correlation with pathologic pregnancy outcome.

To determine correlations between macrophage colony-stimulating factor (MCSF) levels in maternal blood during first trimester screening with respect to normal and pathological pregnancies. This was a prospective single centre study. First trimester screening was performed according to FMF London certificates. Nuchal translucency, PAPP-A and free β-HCG were obtained as well as M-CSF serum levels in maternal blood. Fetal karyotyping was achieved by chorionic villi sampling. 125 patients were enrolled in this study. 21 pregnancies had confirmed aberrant karyotypes. Trisomy 21 cases showed significantly elevated M-CSF levels of 270±91 pg/ml (p=0.032), whereas cases of trisomy 13 (183±68 pg/ml) and trisomy 18 (143±40 pg/ml) had low M-CSF levels. Furthermore M-CSF levels tended to be low in preterm deliveries, placental insufficiency and nicotine consumption. In cases with gestational diabetes M-CSF tended to be elevated. Furthermore we found a positive correlation between high free β-human chorionic gonadotropin (hcg) and MCSF values. There was no correlation between pregnancy associated plasma protein (PAPP-A) and M-CSF. M-CSF is a cytokine promoting placental growth and differentiation. M-CSF is known to be involved in the process of implantation in pregnancy. The role of M-CSF with respect to disturbed pregnancy outcomes such as placental insufficiency in normal or aberrant karyotypes, for example, is yet subject to further research.

Macrophage colony-stimulating factor induces prolactin expression in rat pituitary gland.

We investigated the role of macrophage colony-stimulating factor (M-CSF) in the pituitary gland to understand the effect of M-CSF on pituitary hormones and the relationship between the endocrine and immune systems. When we attempted to establish pituitary cell lines from a thyrotropic pituitary tumor (TtT), a macrophage cell line, TtT/M-87, was established. We evaluated M-CSF-like activity in conditioned media (CM) from seven pituitary cell lines using TtT/M-87 cells. TtT/M-87 proliferation significantly increased in the presence of CM from TtT/GF cells, a pituitary folliculostellate (FS) cell line. M-CSF mRNA was detected in TtT/GF and MtT/E cells by reverse transcriptase-polymerase chain reaction (RT-PCR), and its expression in TtT/GF cells was increased in a lipopolysaccharide (LPS) dose-dependent manner. M-CSF mRNA expression was also increased in rat anterior pituitary glands by LPS. M-CSF receptor (M-CSFR) mRNA was only detected in TtT/ M-87 cells and increased in the LPS-stimulated rat pituitary glands. In rat pituitary glands, M-CSF and M-CSFR were found to be localized in FS cells and prolactin (PRL)-secreting cells, respectively, by immunohistochemistry. The PRL concentration in rat sera was significantly increased at 24 h after M-CSF administration, and mRNA levels significantly increased in primary culture cells of rat anterior pituitary glands. In addition, TNF-α mRNA was increased in the primary culture cells by M-CSF. These results revealed that M-CSF was secreted from FS cells and M-CSF regulated PRL expression in rat pituitary glands.

Macrophage colony‐stimulating factor plays a pivotal role in chemically induced hepatocellular carcinoma in mice

The specific purpose of this study was to investigate the role of macrophage colony-stimulating factor (M-CSF) in initiation and progression of hepatocellular carcinoma using M-CSF-deficient mice. M-CSF-deficient (osteopetrotic: op/op) and their littermate (LM) mice were i.p. injected with diethylnitrosamine (DEN) to induce hepatocellular carcinoma. Twenty-eight weeks after DEN administration, the tumor incidence rate and serum M-CSF levels were assessed. Furthermore, distribution of the activated macrophages and the mRNA expression of CD163 and CD204 were evaluated. Moreover, angiogenesis was analyzed in tumors. In another set of experiments, apoptosis and proliferation of the hepatocytes were examined in the acute phase after DEN administration. Isolated hepatic macrophages were cultured with or without M-CSF, and vascular endothelial growth factor (VEGF) production was assessed by enzyme-linked immunoassay. Tumor incidence was significantly reduced in the op/op compared with the LM mice. Serum M-CSF levels were increased in the carcinogenesis models of the LM mice. Hepatic macrophages were found only in tumors in the op/op but in both normal liver tissue and tumors in the LM mice. In the op/op group, the mRNA expression of inflammatory cytokines was significantly lower compared with the LM mice. Furthermore, apoptosis was significantly increased in the op/op than the LM mice. Angiogenesis increased in liver tumors from the LM compared with the op/op mice. Production of VEGF was greater in the hepatic macrophages incubated with M-CSF compared with those without M-CSF. Thus, M-CSF is involved in the progression of chemically induced hepatocarcinogenesis.

Abstract 1424: Inhibition of M-CSF or MCP-1 expression in tumor cells reduces tumor growth and lung metastasis in a murine mammary cancer model.

Abstract Tumor-associated macrophages, which are derived from the infiltration of circulating bone marrow-derived monocytes, consist primarily of a polarized M2 macrophage population and are associated with poor prognosis in various cancers. We previously observed that solid tumor growth and lung metastasis were enhanced when 4T1 mammary carcinoma cells were injected with M2 macrophages into the mammary fat pad of BALB/c mice. Cancer cell proliferation and macrophage infiltration were markedly increased when M2 macrophages were co-injected with 4T1 cells. In the present study, we explored the mechanisms underlying the crosstalk between 4T1 cells and M2 macrophages in tumor microenvironment. The results of in vitro experiments revealed that the migration of monocytes and the secretion of many cytokines including macrophage-colony stimulating factor (M-CSF) and monocyte chemotactic protein-1 (MCP-1) were increased when 4T1 cells were co-cultured with M2 macrophages, as compared to when the 4T1 cells were cultured alone. The mRNA expression of M-CSF and MCP-1 increased in 4T1 cells when 4T1 cells were co-cultured with M2 macrophages. To investigate the potential roles of M-CSF and MCP-1 in tumor growth and metastasis, 4T1 cells were infected with M-CSF, MCP-1, or control shRNA lentivirus particles and selected with puromycin. 4T1 cells infected with M-CSF shRNA did not grow or metastasize to the lung when injected into the mammary fat pads of BALB/c mice. Inhibition of MCP-1 expression in tumor cells also suppressed 4T1 tumor growth and metastasis, however, the degree of inhibition was much smaller than that of M-CSF inhibition. M-CSF knockdown decreased M2 macrophage (mouse mannose receptor+) population, whereas MCP-1 knockdown decreased the number of both M1 and M2 macrophages in tumor tissues. Taken together, these results indicate that M-CSF and MCP-1 are produced by the crosstalk between 4T1 cells and M2 macrophages, and these cytokines play important roles in mammary tumor progression. Citation Format: Han Jin Cho, Jung Han Yoon Park. Inhibition of M-CSF or MCP-1 expression in tumor cells reduces tumor growth and lung metastasis in a murine mammary cancer model. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1424. doi:10.1158/1538-7445.AM2013-1424

The Role of Macrophage Colony-Stimulating Factor in Patients With Acute Myocardial Infarction

We assessed whether macrophage colony-stimulating factor (M-CSF) levels are associated with left ventricular systolic dysfunction (LVSD) in patients with acute myocardial infarction (AMI). We studied 56 patients with AMI (mean age: 67 ± 12 years) and identified those with clinical (Killip class >II) or echocardiographic signs (ejection fraction ≤45%) of LVSD. We evaluated the established cardiovascular risk factors and measured several cardiovascular biomarkers, including M-CSF. Serum M-CSF concentrations (pg/mL) were significantly increased in patients with both clinical and echocardiographic signs of LVSD (460 ± 265 vs 290 ± 210, P = .0103 and 493 ± 299 vs 287 ± 174, P = .0028, respectively). We found a significant inverse association between M-CSF and ejection fraction (r = -.351, P = .0079). Logistic regression analysis revealed that, among all evaluated clinical and biochemical parameters, the stronger predictor of LVSD was M-CSF (odds ratios 2.1, 95% confidence interval 1.1-2.9, P = .0168). This is the first study reporting plasma M-CSF levels as independent determinants of low LV ejection fraction and clinical LV dysfunction in patients with AMI.

Role of macrophage-colony stimulating factor (M-CSF) on the induction of cFms and proliferating cell nuclear antigen (PCNA) in microglia in vitro

Role of macrophage-colony stimulating factor (M-CSF) on the induction of cFms and proliferating cell nuclear antigen (PCNA) in microglia in vitro