Objective To study the effect of water soluble chitosan (WSC) on the apoptosis of peritoneal macrophage induced by lipopolysaccharides (LPS), and discuss the mechanism. Methods Peritoneal macrophages were divided to three groups: phosphate buffered saline (PBS) group, LPS group and LPS plus WSC group. At hour 24, apoptosis cell and active caspase-3 were detected by flow cytometry; nitric oxide (NO) was determined with Griess reagent. Results There were more apoptosis cells in the LPS group than the PBS group. The percentage of apoptosis cells was significantly decreased in the LPS plus WSC group than the LPS group. The expression of active caspase-3 and the secretion of NO were also inhibited by WSC after LPS intervention. Conclusion WSC inhibits apoptosis of peritoneal macrophage induced by LPS.
63 normal human gallbladders (non-stone group) and 47 inflammed cholesterol stone gallbladders(stone group) were assayed for the amount of macrophages(ΜΦ),the levels of tumor necro-sis factor (TNF) and interleukin 1(1L-1).It was found that in stone group,the amount of ΜΦ was significantly higher than in non-stone group(ΜΦ4101.90±295.72 vs 572.13±30.07AU,Plt;0.01).The levels of TNF and 1L-1 released mainly from the MΦ in stone group were also significantly increased in comparison with those in non-stone group(TNF 18.12±2.03 vs 4.45±0.39ng/mg,Plt;0.001;1L-1 102.42±7.84 vs 66.75±9.50u/mg protein,Plt;0.05).These results suggest that the activited ΜΦ and increases of TNF,1L-1 may be closely related to the inflammatory reaction in gallbladders and the formation of cholesterol gallstones.
Objective To explore the role of macrophage-stimulating protein ( MSP) and receptor tyrosine kinase RON in the airway inflammation of chronic obstructive pulmonary disease( COPD) , and investigate its possible mechanism. Methods The rat COPDmodel was established by exposing the rats to cigarette smoke daily for three months. Rat alveolar macrophages ( AMs) were isolated in vivo and cultured,and then challenged with different concentrations of MSP for 24 hours. The concentrations of MSP in broncho-alveolar lavage fluid ( BALF) and serum, and the levels of IL-1β, TNF-α, IL-8, and IL-10 in the supernatants were measured by ELISA. The expression of RONmRNA in lung tissue was assessed by reverse transcription-polymerase chain reaction. The levels of RON protein in the lung tissue and AMs cultured in vitro were observed by immunohistochemistry. The activity of superoxide dismutase ( SOD) and malondialdehyde ( MDA) content in the culture solution were measured with chromatometry method. Results Compared with the control group, the concentrations of MSP in serum and BALF of the COPD rats were significantly higher ( P lt;0. 01) . The levels of RONmRNA and RON protein in the COPD rats were also upregulated significantly ( P lt; 0. 01) . MSP evoked the AMs isolated from the normal and COPD rats to generate more content of MDA and caused a reduction in activity of SOD. In addition, MSP stimulated TNF-α, IL-8, IL-1βand IL-10 release fromAMs of the normal and COPD rats dose-dependently. The levels of TNF-α, IL-8, and IL-1βwere higher, while the level of IL-10 and the SOD activity were lower in AMs of the COPD group than those of the control group in the same dose of MSP ( P lt;0. 01) . The more significant increase in the levels of TNF-α, IL-8, IL-1β, and the more notable decrease in the activity of SOD was found in the COPD group compared with the control group. But the degree of increasing MDA and IL-10 in the AMs of the COPD group was lower than that in the control group. Linear correlation analysis showed that the MSP concentration and the RON protein level in the COPD rats were positively associated with the total cellcounts and AM counts in BALF, and were related to the indexes for pulmonary emphysema. Conclusions There is a close correlation between the MSP and receptor tyrosine kinase RON with the airway inflammation of COPD. The mechanism might be that MSP promote the macrophages release inflammatory factors and increase the production of oxygen free radicals.
Postmenopausal osteoporosis (PMOP) is a significant metabolic bone disease triggered by estrogen deficiency. Macrophages, as pivotal cells in bone metabolism regulation, participate in bone remodeling and inflammatory modulation through differentiation into osteoclasts and polarization phenotype switching. This article systematically reviews the mechanistic roles of macrophages in PMOP, encompassing their interactions with osteoclasts, polarization effects, immune-inflammatory responses, and impacts of oxidative stress. Furthermore, it explores the potential applications of macrophages in molecular diagnosis and pharmacological interventions for PMOP, while proposing future research directions.
ObjectiveTo investigate the role of Krüppel-like factor 4 (KLF4) mediated monocyte/macrophage subtype switch in the pathological progression of pulmonary fibrosis.MethodsThirty-six patients with interstitial pneumonia were recruited from Characteristic Medical Center of the Chinese People's Armed Police Force between May 2015 and January 2017. Peripheral venous blood and bronchoalveolar lavage fluid were collected in the morning. Pulmonary function and arterial blood gas were tested after admission. Flow cytometry was used to test monocyte subtypes of peripheral blood and macrophage subtypes of bronchoalveolar lavage fluid. KLF4 of peripheral blood was detected by enzyme linked immunosorbent assay. Thirty normal subjects were selected as control group of peripheral blood mononuclear cell subtypes and KLF4 (control group A), and 10 patients without pulmonary fibrosis who needed bronchoscopy were selected as control group of macrophage subtypes in alveolar lavage fluid (control group B). The relationship between the expression of KLF4 and the differentiation of monocytes and macrophages were observed. Furthermore, the relationship between the differentiation of monocytes subtypes, macrophages subtypes and lung function were observed.ResultsMonocyte of CD14++CD16– subtype in pulmonary fibrosis group was significantly lower than that in control group A (P<0.05). Monocyte of CD14++CD16+ subtype in pulmonary fibrosis group was significantly higher than that in control group A (P<0.05). No significant difference was found between the two groups regarding CD14+CD16++. No correlation was found between three subtypes of monocyte and DLCO of patients and between three subtypes of monocyte and PaO2 of patients. M1 macrophage in pulmonary fibrosis group was significantly lower than that in control group B (P<0.05). M2 macrophage in pulmonary fibrosis group was significantly higher than that in control group B (P<0.05). Negative correlation was found between the ratio of M2 subtypes and DLCO of patients and between the ratio of M2 subtypes and PaO2 of patients (P<0.05). KLF4 protein of blood in pulmonary fibrosis group was significantly higher than that in control group A (P<0.05). Positive correlation was found between the ratio of M2 subtypes and KLF4 protein (P<0.05).ConclusionsCD16+ monocyte plays a role in the occurrence and development of pulmonary fibrosis, but no evidence is found there is a direct correlation between monocyte subtypes of peripheral blood and fibrosis degree of lung tissue. M2 macrophage subtype plays an important role in the development of interstitial pneumonia. The number of M2 macrophages is positively correlated with the severity of pulmonary fibrosis. Monocyte/macrophage subtype differentiation by KLF4 may play a role in the pathological progression of pulmonary fibrosis.
ObjectiveTo investigate the changes of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) in rats exposed to paraquat (PQ). MethodsAdult healthy SD rats were randomly divided into a control group (n=8) and three experimental groups (PQ in low dosage of 15 mg/kg,medium dosage of 30 mg/kg,and high dosage of 60 mg/kg,n=24 in each group). The rats in three experimental groups were intragastrically administered with PQ,and the rats in the control group were treated with saline by gavage. Two rats in the control group and six rats in three experimental groups were sacrificed on 1st,7th,14th,and 21st day after exposure respectively. BALF was collected for measurement of interleukin-1(IL-1),IL-6,macrophage inflammatory protein-2(MIP-2),monocyte chemoattractant protein-1(MCP-1),and biopterin by ELISA. ResultsThe levels of cytokines in all experimental groups were higher than those in the control group at any time point. In the exposure day 1 to day 14, IL-1 and biopterin levels in BALF increased significantly with the increase in PQ dose. On 14th and 21st day,IL-6 level in BALF increased significantly with the increase in PQ dosage. The levels of IL-1,IL-6,and biopterin in the experimental groups reached the peak on 14th day. On 14th day,the MIP-2 level in BALF of high-dosage group was significantly higher than that of low-dosage and medium-dosage groups (all P<0.05). The level of MCP-1 in the low-dosage group was lower than that in the medium-dosage and high-dosage groups at any time point (P<0.05). ConclusionIL-1,IL-6,MIP-2,MCP-1,and biopterin may play important roles in the development and progression of PQ-induce lung inflammation.
ObjectiveTo summarize the current advancement of peroxisome proliferator activated receptors (PPARs) participating in formation of abdominal aortic aneurysm (AAA) and to find out the potential treatment strategy of AAA. MethodsRelevant literatures about PPARs and formation of AAA were reviewed. ResultsAAA involved inflammation of all the layers of aorta, and the formation of AAA needed many kinds of inflammatory cells and cytokines. Many researches in vitro or in vivo had shown that PPARs could reduce the expression of inflammatory cytokines, to reduce formation of AAA. However, PPARγ was also confirmed to participate in the formation of AAA and the mechanism might be the transformation of macrophage from type 1 macrophage (M1) to type 2 macrophage (M2). According to the existing studies, the assumption could be that PPARγ can suppress the inflammatory function of M1 to reduce formation of AAA at the initiating stage, and promote formation of AAA by inducing the transform of macrophage to M2 at the late stage. ConclusionPPARs may be a potential targeting point for the prevention of AAA. More studies are needed to show the feasibility and to decide the application timing.
Objective To study the effect of mechanical stretch on the microenvironment of BEAS-2B on macrophage polarization and the role of polarized macrophages in the epithelial-mesenchymal transition (EMT) of BEAS-2B. Methods Using enzyme linked immunosorbent assay to detect the changes in the levels of cytokines such as interferon-γ, granulocyte-macrophage colony stimulating factor, tumor necrosis factor-α, interleukin (IL)-4, IL-6, IL-10 in the supernatant of lung epithelial cells cultured statically and mechanically stretched. The M0 macrophages (derived from THP-1) were stimulated by stretch/static conditioned medium of BEAS-2B. The surface markers of M1 (CD197) /M2 (CD206) macrophages were detected by flow cytometer. Stretch/static conditioned medium were used to stimulate the co-culture system of macrophages and BEAS-2B in the presence or absence of platelet-derived growth factor receptor inhibitor (PDGFRi), then the protein expression level of EMT makers was examined by Western blot. Results Exposure of BEAS-2B to mechanical stretch resulted in significantly higher production of the pro-M1/M2 polarized factor. The EMT of the co-culture system of M0 and BEAS-2B could be induced by stretch conditioned medium, epithelial marker cytokeratin (CK)-8 and E-cadherin were decreased, while mesenchymal marker α-smooth muscle actin, N-cadherin and vimentin were increased in stretch conditioned medium group. The expression of platelet-derived growth factor (PDGF) was significantly higher in stretch conditioned medium group. The PDGFRi can block the EMT in stretch conditioned medium group. Conclusions The lung epithelial cell supernatant induced by mechanical stretch can promote the polarization of macrophages to M1 and M2. Polarized macrophages promote EMT in human lung epithelial cells via PDGF, and blocking PDGF might attenuate the VILI-associated lung fibrosis.
Macrophages are major effecter cells of nonspecific immune response, the polarization of which plays a great role in inflammation, repairing and angiogenesis. According to functional phenotypes, macrophages can be polarized to classically activated type (M1), which could promote angiogenesis, and alternatively activated type (M2), which could inhibit angiogenesis. The proportion of M1/M2 could modulate the growth of choroidal neovascularization (CNV). Under the conditions of aging and injury within the retina, macrophages may polarize to M2, which could generate several proangiogenic factors, initiating and promoting the formation of angiogenesis and fibrous scar. Therefore, regulation of macrophage polarization is expected to inhibit angiogenesis and provide new insight for treatment of CNV.
PURPOSE: To investigate the activation and immune respones of lymphocytes in epiretinal membranes (ERMs)and subretinaI membranes (SRMs). METHODS: A panel of morioclonal antibodies against CD23 (activated B cell), CD25 (activated T cell), CD68(macrophages) and HLA-DR (human leukocyte antigen II antigen)were used for the study of 20 specimens of ERMs from 20 patients with proliferative vitreoretinopathy (PVR),traumatic PVR and secondary traction retinal detachment,and 2 SRMs from PVR and traumatic PVR, with positive and negative reaction specimens as controls. RESULTS:Four cases of ERMs were found to be CD23 and CD25 positive respectively,and one case of SRMs to be CD23 and CD25 positive respectively. All the specimens of ERMs and SRMs revealed CD68 and HLA-DR positive in this series. CONCLUSIONS :There might be an aberrant immunoreaction mediated by T and B cells in the ERMs and the SRMs,and they might play an important role in the patbogenesis of PVR,traumatic PVR and secondary traction retinal detachments. （Chin J Ocul Fundus Dis,1996,12: 147-150）