LncRNA LINC00466 Promotes the Progression of Breast Cancer via miR-4731-5p/EPHA2 Pathway.

BACKGROUND: Breast Cancer (BC) is a female malignancy with a high mortality rate. Novel diagnostic and prognostic biomarkers are valuable for reducing BC mortality. Our study is designed to undrape the precise role of the LINC00466/miR-4731-5p/EPHA2 axis in BC.

Progress in cancer research on the regulator of phagocytosis CD47, which determines the fate of tumor cells (Review).

Cluster of differentiation 47 (CD47) is a transmembrane protein that is widely and moderately expressed on the surface of various cells and can have an essential role in mediating cell proliferation, migration, phagocytosis, apoptosis, immune homeostasis and other related responses by binding to its ligands, integrins, thrombospondin-1 and signal regulatory protein α. The poor prognosis of cancer patients is closely associated with high expression of CD47 in glioblastoma, ovarian cancer, breast cancer, bladder cancer, colon cancer and hepatocellular carcinoma. Upregulation of CD47 expression facilitates the growth of numerous types of tumor cells, while downregulation of its expression promotes phagocytosis of tumor cells by macrophages, thereby limiting tumor growth. In addition, blocking CD47 activates the cyclic GMP-AMP (cGAMP) synthase/cGAMP/interferon gene stimulating factor signaling pathway and initiates an adaptive immune response that kills tumor cells. The present review describes the structure, function and interactions of CD47 with its ligands, as well as its regulation of phagocytosis and tumor cell fate. It summarizes the therapeutics, mechanisms of action, research advances and challenges of targeting CD47. In addition, this paper provides an overview of the latest therapeutic options for targeting CD47, such as chimeric antigen receptor (CAR) T-cells, CAR macrophages and nanotechnology-based delivery systems, which are essential for future clinical research on targeting CD47.

[IL-6 enhances the phagocytic function of mouse alveolar macrophages by activating the JAK2/STAT3 signaling pathway].

Objective To investigate the effect of interleukin-6 (IL-6) on the phagocytosis of MH-S alveolar macrophages and its related mechanisms. Methods A mouse acute lung injury (ALI) model was constructed by instilling lipopolysaccharide (LPS) into the airway. ELISA was used to detect the content of IL-6 in bronchoalveolar lavage fluid (BALF). In vitro cultured MH-S cells, in the presence or absence of signal transducer and activator 3 of transcription(STAT3) inhibitor Stattic (5 µmol/L), IL-6 (10 ng/mL~500 ng/mL) was added to stimulate for 6 hours, and then incubated with fluorescent microspheres for 2 hours. The phagocytosis of MH-S cells was detected by flow cytometry. Western blot analysis was used to detect the expression levels of phosphorylated Janus kinase 2 (p-JAK2), phosphorylated STAT3 (p-STAT3), actin-related protein 2 (Arp2) and filamentous actin (F-actin). Results The content of IL-6 in BALF was significantly increased after the mice were injected with LPS through the airway. With the increase of IL-6 stimulation concentration, the phagocytic function of MH-S cells was enhanced, and the expression levels of Arp2 and F-actin proteins in MH-S cells were increased. The expression levels of p-JAK2 and p-STAT3 proteins increased in MH-S cells stimulated with IL-6(100 ng/mL). After blocking STAT3 signaling, the effect of IL-6 in promoting phagocytosis of MH-S cells disappeared completely, and the increased expression of Arp2 and F-actin proteins in MH-S cells induced by IL-6 was also inhibited. Conclusion IL-6 promotes the expression of Arp2 and F-actin proteins by activating the JAK2/STAT3 signaling pathway, thereby enhancing the phagocytic function of MH-S cells.

Immunoregulatory function of SP-A.

Surfactant protein A (SP-A), a natural immune molecule, plays an important role in lung health. SP-A recognizes and binds microbial surface glycogroups through the C-type carbohydrate recognition domain, and then binds corresponding cell surface receptors (such as C1qRp, CRT-CD91 complex, CD14, SP-R210, Toll-like receptor, SIRP-α, CR3, etc.) through collagen-like region, and subsequently mediates biological effects. SP-A regulates lung innate immunity by promoting surfactant absorption by alveolar type II epithelial cells and phagocytosis of pathogenic microorganisms by alveolar macrophages. SP-A also regulates lung adaptive immunity by inhibiting DC maturation, and T cell proliferation and differentiation. This article reviews latest relationships between SP-A and adaptive and intrinsic immunity.

LINC02086 promotes cell viability and inhibits cell apoptosis in breast cancer by sponging miR-6757-5p and up-regulating EPHA2.

BACKGROUND: Long non-coding RNAs (lncRNAs) are critical regulators in the initiation and progression of breast cancer. Our study aims to characterize the functions of LINC02086 which few published in breast cancer and decipher the downstream molecular mechanisms. METHODS: LINC02086 expression is tested in RNA-seq data from GEPIA database, tumor tissue samples from hospital patients and breast cancer cell lines. LINC02086 was silenced or overexpressed by lenti-virus-mediated shRNAs, or pLVX-Puro plasmids. Luciferase reporter assay and RNA pull-down assay were applied to study interactions between LINC02086, miR-6757-5p and ephrin type-A receptor 2 (EPHA2). LINC02086-silencing MCF-7 cells were injected into mice to establish xenograft animal models. RESULTS: Using RNA-seq data, tumor tissue samples and breast cancer cells, LINC02086 was consistently found to be up-regulated in breast cancer, and correlated with poorer prognosis. LINC02086 knockdown decreased cell viability, promoted cell apoptosis and suppressed tumor growth. LINC02086 interacted with miR-6757-5p that interacted with EPHA2.LINC02086 expression was negatively correlated with miR-6757-5p expression (r = -0.5698, P < 0.001) but was positively correlated with EPHA2 expression (r = 0.5061, P < 0.001). miR-6757-5p expression was negatively correlated with EPHA2 expression (r = -0.5919, P < 0.001). LINC02086 regulated EPHA2 via miR-6757-5p. miR-6757-5p/EPHA2 axis was a mediator of the effect of LINC02086 on cell viability and apoptosis. CONCLUSION: LINC02086 increases cell viability and decreases apoptotic cells in breast cancer by sponging miR-6757-5p to upregulate EPHA2. This study presents LINC02086/miR-6757-5p/EPHA2 axis as promising therapeutic targets for breast cancer intervention.

Interaction of lncRNA Gm2044 and EEF2 promotes estradiol synthesis in ovarian follicular granulosa cells.

The functions and molecular mechanisms of long noncoding RNA (lncRNA) in reproduction have been widely studied at present. However, lncRNA regulating hormone synthesis in ovarian follicular granulosa cells has not been sufficiently studied. Our previous research demonstrated that lncRNA Gm2044 could promote estradiol synthesis in follicular granulosa cells. In this study, we identified 21 binding proteins of lncRNA Gm2044 in ovarian follicles using comprehensive identification of RNA-binding proteins by mass spectrometry (ChIRP-MS). RNA immunoprecipitation (RNA IP) and reverse transcription PCR (RT-PCR) confirmed that lncRNA Gm2044 can interact with eukaryotic translation elongation factor 2 (EEF2) protein. Furthermore, we constructed lncRNA Gm2044 knockout mice using the CRISPR/Cas9 method. Although the follicular development and fertility of female lncRNA Gm2044 knockout mice were not affected, the serum estradiol concentration in female lncRNA Gm2044 knockout mice significantly decreased. Western blotting and ELISA revealed that lncRNA Gm2044 may promote the binding of EEF2 to Nr5a1 mRNA and then enhance the Nr5a1 mRNA translation, and the upregulated NR5A1 protein can strengthen estradiol synthesis. To determine the potential signaling pathway of lncRNA Gm2044 regulating estradiol synthesis, transcriptome sequencing was performed for ovaries of adult lncRNA Gm2044 knockout mice, which identified 565 significant up-regulated genes and 303 significant down-regulated genes, which were then analyzed with Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) and validated by molecular experiments. Understanding how lncRNA Gm2044/EEF2 protein regulates estradiol synthesis will help treat estrogen-related reproductive diseases.

Role of GM-CSF in lung balance and disease.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic growth factor originally identified as a stimulus that induces the differentiation of bone marrow progenitor cells into granulocytes and macrophages. GM-CSF is now considered to be a multi-origin and pleiotropic cytokine. GM-CSF receptor signals activate JAK2 and induce nuclear signals through the JAK-STAT, MAPK, PI3K, and other pathways. In addition to promoting the metabolism of pulmonary surfactant and the maturation and differentiation of alveolar macrophages, GM-CSF plays a key role in interstitial lung disease, allergic lung disease, alcoholic lung disease, and pulmonary bacterial, fungal, and viral infections. This article reviews the latest knowledge on the relationship between GM-CSF and lung balance and lung disease, and indicates that there is much more to GM-CSF than its name suggests.

[CXCL1 induces the contraction of endothelial cytoskeleton and increases permeability in mouse cerebral endothelium bEND.3 cells by promoting protein kinase B phosphorylation].

Objective To investigate the effects of C-X-C motif chemokine ligand 1 (CXCL1) and its receptor CXCR2 on the cerebral endothelial cytoskeleton rearrangement and permeability in the inflammation of septic encephalopathy. Methods The murine model of septic encephalopathy was established by intraperitoneal injection of LPS (10 mg/kg). The levels of TNF-α and CXCL1 in the whole brain tissue were detected by ELISA. The expression of CXCR2 was detected by Western blot analysis after bEND.3 cells were stimulated with 500 ng/mL LPS and 200 ng/mL TNF-α. After treated with CXCL1(150 ng/mL), the changes of endothelial filamentous actin (F-actin) rearrangement in bEND.3 cells were observed by immuno-fluorescence staining. In the cerebral endothelial permeability test, bEND.3 cells were randomly divided into PBS control group, CXCL1 group, and CXCL1 combined with CXCR2 antagonist SB225002 group. Then endothelial transwell permeability assay kit was used to detect the endothelial permeability changes. After stimulated with CXCL1 in bEND.3 cells, Western blot analysis was used to detect the expression of protein kinase B (AKT) and phosphorylated-AKT (p-AKT). Results Intraperitoneal injection of LPS significantly increased the levels of TNF-α and CXCL1 in the whole brain. LPS and TNF-α both upregulated the expression of CXCR2 protein in bEND.3 cells. CXCL1 stimulation induced the endothelial cytoskeleton contraction, increased paracellular gap formation and elevated endothelial permeability in bEND.3 cells, which was inhibited by the pretreatment with SB225002(CXCR2 antagonist). Furthermore, CXCL1 stimulation also enhanced the phosphorylation of AKT in bEND.3 cells. Conclusion CXCL1 induces the cytoskeleton contraction and increased permeability through AKT phosphorylation in bEND.3 cells, which can be effectively inhibited by CXCR2 antagonist SB225002.

Activation of Nrf2 modulates protective immunity against Mycobacterium tuberculosis infection in THP1-derived macrophages.

Tuberculosis (TB), caused by mycobacterium tuberculosis (M. tuberculosis) infection, is one of the leading causes of death globally and poses a threat to public health. During infection, M. tuberculosis causes redox imbalance and dysfunctions of protective immunity. Transcription factor nuclear factor erythroid 2 (NF-E2)-related factor (Nrf2) is a major modulator of cellular redox homeostasis via transcriptional induction of cytoprotective genes to protect cell against the damage from insults. Thus, we hypothesize that Nrf2 may regulate protective immunity against M. tuberculosis. RNA-seq and immunoblotting results suggested that the expression of Nrf2 protein increased after M. tuberculosis infection, and decreased upon long-term M. tuberculosis infection, while Keap1 protein maintained a low expression level during M. tuberculosis infection. Furthermore, Nrf2 activator sulforaphane (SFN) decreased proinflammatory cytokines production, phagocytosis and host cell apoptosis, while increasing ROS levels and promoting autophagy in THP1 macrophages infected with M. tuberculosis. In addition, SFN-activated Nrf2 augmented bacterial killing by macrophages, which might be due to the regulation of protective immunity via Nrf2. Combined, our results extend the understanding of the complex innate immunity regulation by Nrf2 against mycobacterial infection. Also, these findings suggested that the regulation of Nrf2 signaling cascade could be used as a therapeutic target for the treatment of TB patients and the development of better anti-TB vaccines.

PGE2 inhibits neutrophil phagocytosis through the EP2R-cAMP-PTEN pathway.

Prostaglandin E2 (PGE2) is a potent lipid mediator of inflammation that modulates immune cell function by binding to unique G protein-coupled receptors (EP receptors). PGE2 production increases during microbial infection and inflammation. In this study, we assessed the effect of PGE2 on the phagocytosis of bacteria by neutrophils, which are key players during infection and inflammation. We also looked for specific EP receptor signaling pathways that contributed to the neutrophil phagocytic activity. PGE2 (50-1000 ng/ml) inhibited the phagocytosis of Escherichia coli by HL-60 human neutrophils in a concentration-dependent manner. Inhibition of neutrophil phagocytosis by PGE2 correlated with increased intracellular cyclic adenosine monophosphate (cAMP) production, and forskolin, an adenosyl cyclase agonist, confirmed the inhibitory effect of cAMP stimulation on neutrophil phagocytosis. The expression of EP2 receptors by HL-60 cells was confirmed by western blot analysis, and selective agonism of EP2 receptors mimicked the inhibition of phagocytosis by PGE2. The EP2 receptor antagonist AH-6089 partially blocked the inhibition of neutrophil phagocytosis PGE2. Specific inhibition of phosphatase and tensin homolog (PTEN) enzyme attenuated the inhibition of neutrophil phagocytosis by PGE2, and both PGE2 and increased intracellular cAMP increased neutrophil PTEN activity, which was associated with decreased PTEN phosphorylation. The results support negative regulation of the antimicrobial activity of neutrophils (i.e., phagocytosis), which has important implications for the future management of bacterial infections.

[IGF-1 activates the PI3K pathway through S1P/S1PR1 signaling to promote the migration of mouse alveolar epithelial cells].

Objective To investigate the effect of insulin-like growth factor 1 (IGF-1) on the migration of alveolar epithelial cells (AECs) and its related mechanisms. Methods The MLE-12 cells (mouse AEC line) were stimulated by IGF-1 and sphingosine 1 phosphate (S1P) in the presence or absence of the PI3K inhibitor Wortmannin. Then, the cell migration was detected by the scratch test and the expression of p-Akt was detected by Western blot. With AECs stimulated by IGF-1, the secretion and expression of S1P were tested by ELISA and Western blot respectively. In the blocking experiment, the effect of IGF-1 on cell migration or p-Akt expression was detected by scratch test or Western blot after the interference of AEC S1P receptor 1 (S1PR1) or the action of S1PR1 blocking antibody. Results After 12 hours of IGF-1 stimulation, the expression of p-Akt in AECs increased and the migration of AECs accelerated. When blocking PI3K signal, the effect of IGF-1 on promoting AEC migration was partially eliminated. IGF-1 induced AECs to produce S1P, which accelerated AEC migration through S1PR1. The expression of p-Akt in AECs increased after S1P stimulation. When blocking the PI3K pathway, the ability of S1P to accelerate the migration of AECs was reduced. When S1PR1 in AECs was blocked or interfered, the effect of IGF-1 on accelerating AEC migration and promoting AEC p-Akt expression was partially reduced. Conclusion IGF-1 activates the PI3K pathway through S1P-S1PR1 signal to promote the migration of AECs.

Trained immunity contributes to the prevention of Mycobacterium tuberculosis infection, a novel role of autophagy.

Mycobacterium tuberculosis (M. tuberculosis) is the pathogen which causes tuberculosis (TB), a significant human public health threat. Co-infection of M. tuberculosis and the human immunodeficiency virus (HIV), emergence of drug resistant M. tuberculosis, and failure to develop highly effective TB vaccines have limited control of the TB epidemic. Trained immunity is an enhanced innate immune response which functions independently of the adaptive/acquired immune system and responds non-specifically to reinfection with invading agents. Recently, several studies have found trained immunity has the capability to control and eliminate M. tuberculosis infection. Over the past decades, however, the consensus was adaptive immunity is the only protective mechanism by which hosts inhibit M. tuberculosis growth. Furthermore, autophagy plays an essential role in the development of trained immunity. Further investigation of trained immunity, M. tuberculosis infection, and the role of autophagy in this process provide new possibilities for vaccine development. In this review, we present the general characteristics of trained immunity and autophagy. We additionally summarize several examples where initiation of trained immunity contributes to the prevention of M. tuberculosis infection and propose future directions for research in this area.

Vascular Endothelial Growth Factor Inhibits Phagocytosis of Apoptotic Cells by Airway Epithelial Cells.

Professional phagocytes such as dendritic cells and macrophages can ingest particles larger than 0.5 µm in diameter. Epithelial cells are nonprofessional phagocytes that cannot ingest pathogenic microorganisms, but they can ingest apoptotic cells. Inhibition of the engulfment of apoptotic cells by the airway epithelium can cause severe airway inflammation. Vascular endothelial growth factor (VEGF) is an angiogenesis-promoting factor that can mediate allergic airway inflammation and can promote airway epithelial cells (AECs) proliferation, but it is not clear whether it affects the engulfment of apoptotic cells by AECs. In the present study, VEGF inhibited engulfment of apoptotic cells by AECs via binding to VEGF receptor(R)2. This inhibitory effect of VEGF was not influenced by masking of phosphatidylserine (PS) on the surface of apoptotic cells and was partially mediated by the PI3K-Akt signaling pathway. VEGF inhibition of phagocytosis involved polymerization of actin and downregulation of the expression of the phagocytic-associated protein Beclin-1 in AECs. Since engulfment of apoptotic cells by AECs is an important mechanism for airway inflammation regression, VEGF inhibition of the engulfment of apoptotic cells by airway epithelial cells may be important for mediating allergic airway inflammation.

Alveolar Epithelial Cells Promote IGF-1 Production by Alveolar Macrophages Through TGF-ß to Suppress Endogenous Inflammatory Signals.

To maintain alveolar gas exchange, the alveolar surface has to limit unnecessary inflammatory responses. This involves crosstalk between alveolar epithelial cells (AECs) and alveolar macrophages (AMs) in response to damaging factors. We recently showed that insulin-like growth factor (IGF)-1 regulates the phagocytosis of AECs. AMs secrete IGF-1 into the bronchoalveolar lavage fluid (BALF) in response to inflammatory stimuli. However, whether AECs regulate the production of IGF-1 by AMs in response to inflammatory signals remains unclear, as well as the role of IGF-1 in controlling the alveolar balance in the crosstalk between AMs and AECs under inflammatory conditions. In this study, we demonstrated that IGF-1 was upregulated in BALF and lung tissues of acute lung injury (ALI) mice, and that the increased IGF-1 was mainly derived from AMs. In vitro experiments showed that the production and secretion of IGF-1 by AMs as well as the expression of TGF-ß were increased in LPS-stimulated AEC-conditioned medium (AEC-CM). Pharmacological blocking of TGF-ß in AECs and addition of TGF-ß neutralizing antibody to AEC-CM suggested that this AEC-derived cytokine mediates the increased production and secretion of IGF-1 from AMs. Blocking TGF-ß synthesis or treatment with TGF-ß neutralizing antibody attenuated the increase of IGF-1 in BALF in ALI mice. TGF-ß induced the production of IGF-1 by AMs through the PI3K/Akt signaling pathway. IGF-1 prevented LPS-induced p38 MAPK activation and the expression of the inflammatory factors MCP-1, TNF-α, and IL-1ß in AECs. However, IGF-1 upregulated PPARγ to increase the phagocytosis of apoptotic cells by AECs. Intratracheal instillation of IGF-1 decreased the number of polymorphonuclear neutrophils in BALF of ALI model mice, reduced alveolar congestion and edema, and suppressed inflammatory cell infiltration in lung tissues. These results elucidated a mechanism by which AECs used TGF-ß to regulate IGF-1 production from AMs to attenuate endogenous inflammatory signals during alveolar inflammation.

CXCR2 antagonist attenuates neutrophil transmigration into brain in a murine model of LPS induced neuroinflammation.

Sepsis-associated encephalopathy (SAE) is a devastating neurological complication of sepsis with intolerable high motility. SAE is accompanied with brain vascular injury, endothelial hyperpermeability, and neutrophil infiltration into the brain tissue, key inflammatory processes leading to further brain edema and neuronal cell apoptosis. Recent studies from us and others suggest that the chemokine receptor C-X-C Motif Chemokine Receptor 2 (CXCR2) is crucial for neutrophil recruitment during SAE. Here we use CXCR2 antagonist SB225002 to characterize the role of CXCR2 in brain infiltration of neutrophil in a murine model of SAE. Systemic administration of high-dose LPS (10 mg/kg) induced evident neutrophil infiltration into the cerebral cortex in wild-type mice. However, CXCR2 antagonist SB225002 markedly attenuated neutrophil infiltration into brain. The CXCR2 expression on neutrophils in the peripheral circulation was dramatically downregulated in response to this LPS dose, and endothelial CXCR2 was significantly upregulated, suggesting endothelial but not neutrophil CXCR2 plays a more important role in neutrophil infiltration into brain. Strikingly, although these CXCR2 antagonist SB225002 treated mice displayed reduced neutrophil infiltration, no change in neutrophil rolling and adhesion was observed. Furthermore, we confirmed that CXCR2 agonist CXCL1 induced a marked increase in actin stress fiber synthesis and paracellular gap formation in cultured cerebral endothelial cells, which is attenuated by SB225002. Thus, these results demonstrate a selective role for endothelial CXCR2 to regulate cerebral vascular permeability and neutrophil transmigration in high-dose LPS induced neuroinflammation, and also suggest a therapeutic potential of CXCR2 antagonist SB225002 in SAE.

Yes-associated protein upregulates filopodia formation to promote alveolar epithelial-cell phagocytosis.

Cells engulf particles larger than 0.5 µm in diameter by phagocytosis, which is driven by cytoskeletal rearrangements. Phagocytosis by alveolar epithelial cells (AECs) helps to maintain the alveolar homeostasis. Yes-associated protein (YAP), a transcriptional coactivator of the Hippo pathway, affects proliferation, differentiation, and cytoskeletal rearrangement of AECs, but it is not clear whether YAP regulates phagocytosis. In this study, interference with YAP expression inhibited phagocytosis in MLE-12 cells and in primary cultures of AEC. Filopodia formation promoted phagocytosis in AECs, and YAP enhanced filopodia formation in AECs. Blocking PI3K signaling resulted in reduced YAP protein expression and inhibition of phagocytosis. The results indicate that YAP expression was regulated by PI3K signaling and promoted phagocytosis in AECs by upregulating filopodia formation.

LPS restores protective immunity in macrophages against Mycobacterium tuberculosis via autophagy.

Autophagy has been identified as an important immune regulatory mechanism. Recent studies have linked macrophage autophagy with innate immune responses against Mycobacterium tuberculosis (M. tuberculosis), which can survive within macrophages by blocking fusion of the phagosome with lysosomes. These findings suggest that autophagy is a regulatable cellular mechanism of M. tuberculosis defense in macrophages. Transcriptomic profiles in human blood in TB patients suggest that M. tuberculosis affects autophagy related pathways. In order to better understand the role of macrophage autophagy in enhancing protective immunity against M. tuberculosis, in this study, we investigate the effects of the autophagy activators rapamycin and LPS in macrophage autophagy and immunity against M. tuberculosis. We confirm that rapamycin and LPS induce autophagy in M. tuberculosis infected THP-1-derived macrophages or PMA primed THP-1 macrophages [THP-1(A)]. LPS restores M. tuberculosis-inhibited IL-12 synthesis and secretion in THP-1(A) cells via autophagy. Similarly, autophagy activators increase IL-12 synthesis and secretion in THP-1(A) cells. These studies demonstrate the importance of autophagy in M. tuberculosis elimination in macrophages and may lead to novel therapies for tuberculosis and other bacterial infections.

[Phagocytosis of alveolar macrophages is suppressed in a mouse model of lipopolysaccharide-induced acute lung injury].

OBJECTIVE: To investigate the changes in phagocytic function of alveolar macrophages (AMs) in mice with lipopolysaccharide (LPS)-induced acute lung injury (ALI) and explore the possible mechanism. METHODS: Kunming mice were randomly divided into normal control group and ALI (induced by LPS instillation in the airway) model group. AMs were obtained from bronchoalveolar lavage fluid in both groups, and phagocytosis of the AMs was observed using flow cytometry and fluorescence microscopy. Western blotting and ELISA were used to detect the expression and secretion of IL-33 in the lung tissue of the mice. We also detected the secretion of IL-33 by an alveolar epithelial cell line MLE-12 in response to stimulation with different concentrations of LPS. The AMs from the normal control mice were treated with different concentrations of LPS and IL-33, and the changes in the phagocytic activity of the cells were observed. RESULTS: Compared with those in normal control group, the percentage of AMs phagocytosing fluorescent microspheres was significantly decreased, and the expression of IL-33 in lung tissue and IL-33 level in the bronchoalveolar lavage fluid were significantly increased in ALI mice (P < 0.01). LPS (100-1000 ng/mL) obviously promoted the secretion of IL-33 in cultured MLE-12 cells (P < 0.01). Both LPS (10-500 ng/mL) and IL-33 (100 ng/mL) significantly inhibited the phagocytic activity of the AMs from normal control mice (P < 0.01). CONCLUSIONS: The phagocytic activity of AMs is weakened in ALI mice possibly due to direct LPS stimulation and the inhibitory effect of the alarmin IL-33 produced by LPS-stimulated alveolar epithelial cells.