Effects of insulin on osteoblast and its post-receptor mechanism

AIM:To study the effects of insulin on the proliferation and function of osteoblasts and the relationship between insulin post-receptor change in osteoblasts and osteoblastic cell growth.METHODS:The effects of different levels of insulin on osteoblasts were assessed by MTT colorimetry.Osteocalcin in medium was measured by RIM.IGF-1 mRNA expression levels were determined by RT-PCR.The concentrations of free IGF-1 protein in serum-free medium were measured by ELISA.In addition,the protein level and phosphorylated protein of P44/42MAPK were determined by Western blotting analysis.RESULTS:Insulin enhanced the proliferation of osteoblasts,depending on its dose and exposure time.Insulin at concentration of 10-7 mol/L showed the strongest effect,and the action attained the plateau phase beyond 96 h.The best concentration that stimulated synthesis of osteocalcin by insulin was 10-7 mol/L.When the insulin concentration beyond 10-7 mol/L,the osteocalcin concentration was decreased.Exposure time had no effect on insulin-stimulated synthesis of osteocalcin of osteoblastic cells.When the concentration of insulin reaches 10-6 mol/L,the IGF-1 mRNA expression stimulated by insulin was also decreased.The concentrations of free IGF-1 protein in insulin-stimulated groups were all higher than that in control group (P<0.05),but there was no statistically significant difference among insulin-stimulated groups (P>0.05).Insulin acute stimulation rapidly induced the activity of tyrosine phosphorylation of P44/42MAPK.The degree of tyrosine phosphorylation of P44/42MAPK was increased step by step along with the increasing doses of insulin from 0 to 10-7 mol/L (P<0.05,between groups).After insulin chronicity treatment,there was a marked reduction in the tyrosine phosphorylation of P44/42 MAPK (P<0.05,between groups).There was no significant change in protein level of P44/42MAPK.CONCLUSIONS:Insulin enhances the proliferation of osteoblasts as a growth factor at a suitable concentration,but this effect disappears at chronic high insulin stimulation.The MAPK may be involved in the proliferating effect of insulin on osteoblasts.Transient stimulation of insulin activates the P44/42MAPK,however chronic high insulin stimulation results in down-regulation of P44/42MAPK signal activity.     

Effects of nicotine on activation of PMNs and the ICAM-1 mRNA expression of HUVEC

AIM: To investigate the effects of nicotine on activation of PMNs, adhesion of PMNs-HUVEC and expression of ICAM-1 mRNA in HUVEC. METHODS: Activation of PMNs was measured by detecting the activity of β-glucuronidase and lysozym of PMNs. Adhesion of PMNs and HUVEC was observed. Northern blot was conducted for quantitating ICAM-1 mRNA. RESULTS: Nicotine could increase the activity of β-g [(8.76± 1.01)μg/10⁷·h vs(14.87±2.00)μg/10⁷·h,P<0.05]and Lysozym [(20.0±1.5)μg/10⁷·h vs(36.5±4.4)μg/10⁷·h,P<0.05], and also could promote adhesion of PMNs-HUVEC(38.5±9.8 vs 61.0±4.4,P＜0.05). The expression of ICAM-1 mRNA was induced by nicotine in dose-dependent fashion (10^-5-10^-3mol/L).After a 2 h treatment of HUVEC with nicontine(10^-4mol/L), the level of ICAM-1 mRNA is above the control(1.23 vs 1.63) and the highest level (2.03) is at a 12 h treatment. 764-3 can obviously counteract the above effect of nicotine. CONCLUSIONS: Nicotine could activate PMNs, enhance adhesion of PMNs-HUVEC and increase the expression of ICAM-1 mRNA in HUVEC.     

Effects of oxidative modification of lipoproteins on blood coagulation and fibrinolysis

AIM: To study the effects of oxidative modification lipoproteins on blood coagulation and fibrino-lysis in vitro. METHODS: Normal human plasma VLDL, LDL and HDL, which were isolated by density gradient ultracentrifugation method, were oxidatively modified by Cu²⁺ and HOCl method. N-VLDL, Ox-VLDL, N-LDL, Ox-LDL, N-HDL, Ox-HDL were added to the reaction system which consisted of mixed fresh normal plasma respectively, prothrombin time (PT), activated partial thrombplastin time (APTT), plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (t-PA) and platelet aggregation were measured according to the direction of the kits. RESULTS: The relative electrophoretic mobility (REM), absorbance at 234nm and TBARS of oxidized VLDL, LDL and HDL mediated by HOCl or Cu²⁺ were significantly higher than that of the control group (P<0.01). N-VLDL, N-LDL and N-HDL had no effect on PT, APTT, t-PA, PAI-1 and platelet aggregation. The PT and APTT of Ox-VLDL, Ox-LDL and Ox-HDL were significantly shorter than that of the control group (P<0.05 and P<0.01). The platelet aggregation of Ox-VLDL, Ox-LDL and Ox-HDL were significantly stronger than that of the control group (P<0.01). The Ox-VLDL and Ox-LDL were higher in t-PA and lower in PAI-1 than that of the control group (P<0.05 and P<0.01), but the Ox-HDL had no influences on t-PA and PAI-1 activity. CONCLUSIONS: N-VLDL, N-LDL and N-HDL have no effects on blood coagulation and fibrinolysis in vitro. Ox-VLDL, Ox-LDL and Ox-HDL enhance blood coagulation and thrombosis. Ox-VLDL and Ox-LDL enhance t-PA activity and decreased PAI-1 activity, but Ox-HDL does not affect the fibrinolysis activity.     

Antitumor activity of Paecilomyces tenuipes polysaccharide and its mechanism in vitro

AIM:To investigate the antitumor activity and mechanism of Paecilomyces tenuipes polysaccharide(PTPS).METHODS:PTPS-I was obtained by water extraction and alcohol precipitation, and purified by DEAE-cellulose and Sephadex G-100 chromatography. Human erythroleukemia cell line K562, laryngocarcinoma cell line Hep2 and hepatic carcinoma cell line SMMC-7721were co-cultured with PTPS-I or the conditioned medium which prepared with PTPS-I-stimulated human mononuclear cells (PTPS-I-MNC-CM), and the proliferation of tumor cells was determined. The cell counting kit-8 (CCK-8) was used to determine the proliferation of MNCs. The FQ-RT-PCR was applied to investigate the expression of TNF-α and IL-6 mRNA in MNCs. RESULTS:PTPS-I-MNC-CM inhibited the proliferation of K562, Hep2 and SMMC-7721 cells in vitro (P<0.01). Cytotoxicity of PTPS-I against K562, Hep2 and SMMC-7721 cells was not observed (P<0.01). PTPS-I stimulated the proliferation of MNCs (P<0.01) and significantly enhanced the expression of TNF-α and IL-6 mRNA in MNCs (P<0.05, P<0.01). CONCLUSION:The results suggest that PTPS-I is an immunomodulator and its antitumoral activity is through the immunomodulatory mechanism rather than the direct cytotoxicity against tumor cells.     

The mitogenic activity decline of a haFGF mutant and its mechanism

AIM: To observe the effects of the human acidic fibroblast growth factor mutant (mhaFGF)， lacking 27 amino acids at N-terminal， on the proliferation and signal transduction of the hepatocarcinoma cells. METHODS: The hepatocarcinoma cells were treated with human acidic fibroblast growth factor (haFGF) and mhaFGF, respectively. The expression levels of the signal proteins, Grb2 and Erk1/2, in the hepatocarcinoma cells were detected by semi-quantitative Western-blotting after treated for 15 min. The mitogenic activity of both haFGF and mhaFGF was detected by MTT method and the cell cycle was analysed by flow cytometer (FCM) after treated for 48 h. RESULTS: The mitogenic activity and the ratio of G1 and S phase cells in mhaFGF-treated cells were markedly lower than that of the haFGF, and close to that of the control group. The expression level of both Grb2 and Erk1/2 in the mhaFGF-treated cells were lower than those in the haFGF- treated cells. CONCLUSION: The decrease in the mitogenic activity of mhaFGF is probably associated to its down-regulating the expression of the signal molecular, MAPK-ERK1/2 and Grb2.     

Effects of enalapril on inflammation in kidney of diabetic rats and its possible mechanism

AIM: To investigate the effects and mechanism of enalapril on nephritis of diabetic mice. METHODS: Diabetes was induced by injection of streptozotocin after uninephrectomy. Rats were randomly divided into three groups: control, diabetes, diabetes treated with enalapril (10 mg·kg-1·d-1 by gavage). 8 weeks after STZ injection, urine albumin excretion rate (AER) were measured, and glomerular morphology were observed by light microscopy. The levels of malonyldialdehyde (MDA) in renal tissue and urine as well as activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX) in renal tissue were determined. Immunohistochemistry for ED-1 (macrophage marker), monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule-1 (ICAM-1) were performed by streptavidin-biotin complex (SABC) technique. RESULTS: Increased kidney weight, ratio of kidney weight to body weight, AER and expansion of mesangial as well as tuft areas on histological examination of the kidney were significantly attenuated by the treatment of enalapril (P<0.05, P<0.01). Elevated MDA levels in renal tissue and urine as well as decreased SOD, CAT, GSH-PX activities in renal tissue were also remitted by enalapril (P<0.05). Increased glomerular macrophage recruitment and expression of MCP-1 was significantly inhibited by enalapril (P<0.05). However, elevated ICAM-1 expression was not reduced by enalapril in glomerulus in diabetic rats. CONCLUSION: Possible mechanism of renal protection of enalapril may be at least partly related with suppression of inflammation in kidney of diabetic rats.     

Effects of BTEB2 antisense gene transfection on the proliferation of vascular smooth muscle cells and its mechanism

AIM: To study the effects of BTEB2 antisense RNA on the proliferation of vascular smooth muscle cells(VSMC) and its mechanism. METHODS: After the recombinant adenovirus Ad.ASBTEB2 infected VSMC, antisense RNA and protein expression of BTEB2 were evaluated respectively by RT-PCR and Western blotting. Proliferation and cell cycle progress of VSMC were analyzed respectively by MTT test and flow cytometry. The expression of PCNA, AT1R and PDGF-BB were detected by immunocytochemistry. RESULTS: The expression of BTEB2 antisense RNA was demonstrated in VSMC after infected by recombinant adenovirus. Ad.ASBTEB2 infection significantly inhibited BTEB2 protein expression and proliferation of VSMC induced by serum, and resulted in G0/G1 blocking. The inhibitory effects of BTEB2 antisense RNA on the expression of PCNA, AT1R and PDGF-BB were demonstrated by immunohistochemistry. CONCLUSION: BTEB2 antisense RNA significantly inhibits the proliferation of VSMC, probably by suppressing the expression of VSMC proliferation related genes, such as PCNA, AT1R and PDGF-BB.     

梨对黑星病的抗病性及其机理研究进展

从梨黑星病(Venturia nashicola)病原菌、发病条件、抗病性及抗病机制等方面对梨黑星病的抗病性及其抗性机理研究进行了系统综述。表明,梨黑星病的病原菌有2种,侵染中国梨的为纳雪黑星菌(Venturia nashicola Tanaket Yamamota),侵染西洋梨的为梨黑星菌(Venturia pirina Aderh);梨对黑星病的抗性呈显性遗传,抗病性对感病性为显性;目前,对梨黑星病的抗性机理尚不清楚。     

Effects of leptin on hypoxia-induced apoptosis in cultured alveolar typeⅡ cells of fetal rat and its mechanism

AIM: To investigate the effects of leptin (LEP) on the alveolar type Ⅱ cells(AECⅡ) apoptosis induced by Na₂S₂O₄ and explore the molecular mechanisms. METHODS: Primary AECⅡ culture was prepared according to a specific immunosorption procedure with slight modification and the cells were identified by transmission electron microscope and immunocytochemistry. AECⅡ damage was induced by 5 mmol/L Na₂S₂O₄. LEP group cells were treated with LEP at concentrations from 100 μg/L to 1 600 μg/L. The cell survival rate was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Cell cycle and apoptosis were analyzed by flow cytometry and the level of caspase-3 was measured by Western blotting. RESULTS: Highly purified AECⅡ, obtained by the method of modified immunosorption, were identified with the positive expression of SP-A and intracellular lamellarbodies were found under electron micrography. The cells, exposed to 5 mmol/L Na₂S₂O₄, showed characteristic changes of apoptosis and activation of caspase 3. These damages were relieved by the treatment of LEP (100-1 600 μg/L), with survival increasing, apoptosis peak decreasing, cell morphology restoring and caspase 3 activation inhibiting.CONCLUSION: Leptin prevents AECⅡ from apoptosis induced by Na₂S₂O₄ or hypoxia. The potential mechanism of its action may be related to promoting cell cycle from G₁ phase to S phase and inhibiting the activating of caspase 3.     

Effects of BCL6B on proliferation and migration of human colorectal carcinoma LoVo cells and its potential mechanism

AIM: To detect the endogenous expression of B-cell leukemia/lymphoma 6 member B (BCL6B) in FHC and LoVo cells, and to investigate the effects of BCL6B on proliferation and migration of LoVo cells for further exploring the underlying mechanism. METHODS: The endogenous expression of BCL6B in the FHC and LoVo cells was detected by RT-PCR and Western blot. The methods of MTT assay, colony formation assay, wound healing assay and Transwell chamber experiment were employed to examine the biological functions of BCL6B in the LoVo cells. The mRNA and protein levels of BCL6B, cyclin D1 and matrix metalloproteinase-9 (MMP-9) were determined by RT-PCR and Western blot, respectively. The level of phosphorylated protein kinase B (p-AKT) was detected by Western blot. RESULTS: BCL6B expression was notably repressed in the LoVo cells as compared with the FHC cells, which were significantly increased by transfection with pcDNA3.1-BCL6B. The abilities of proliferation and migration of the LoVo cells at 72 h were inhibited by 28.33%(P<0.01) and 36.11%(P<0.05) in BCL6B group. The mRNA levels of cyclin D1 and MMP-9 in the cells of BCL6B group were decreased by 39.90%(P<0.01) and 77.36% (P<0.05), and the protein levels of cyclin D1, MMP-9 and p-AKT were reduced by 44.00%(P<0.05), 47.06%(P<0.01) and 32.88% (P<0.05), respectively. CONCLUSION: BCL6B inhibits proliferation and migration of the LoVo cells, and the PI3K/AKT signaling pathway is involved in this process.     

Inhibitory effect of JIP on AP-1 activity induced by LMP1 in nasopharyngeal carcinoma cells and its mechanism

AIM: To investigate the mechanism of the AP-1 signal transduction pathway inhibited by JIP in nasopharyngeal carcinoma cells. METHODS: AP-1 activity was triggered by Dox-induced LMP1 expression in Tet-on-LMP1-HNE₂ cells (L7). The retention of phospho-JNK in the cytoplasm caused by JIP was examined with immunofluroscence assay. RESULTS: 24 h after transfection of L7 cells with the JIP expression plasmid, the translocation of activated JNK was inhibited, which resulted in the retention of phospho-JNK in the cytoplasm and down-regulation of the AP-1 activity. CONCLUSION: JIP down-regulates the activity of AP-1 through the inhibition of the translocation of JNK.     

Prevention of isinglass on the chronic atrophic gastritis in rats and its mechanism

AIM: To evaluate the effect of isinglass on chronic atrophic gastritis(CAG) in rats and its mechanism. METHODS: An animal model of CAG in accordance with the previous experience of combined administration of 60% ethanol, 20 mmol/L sodium deoxycholate and 0.1% ammonia water was established in SD rats. Isinglass was used as preventive therapy while we were establishing CAG rat model. Finally all the rats were executed and pathologic changes of the gastric mucosa were studied by gross appearance and microscopy and serum epidermal growth factor (EFG) and growth hormone(GH) contents were tested. RESULTS: In each isinglass prevention group, inflammation grade of gastric antrum was less than that in model group (P<0.01) while the mean ratio of the thickness of gastric mucosal gland and muscularis mucosa (L1/L2), the number of gastric glands in 1 mm lengths of mucosal layer in longitudinal sections were much better than those in model group (P<0.01).They were very close to normal control group (P>0.05). The expression of proliferating cell nuclear antigen (PCNA) in gastric mucosa and serum EFG level were higher than those in model group (P<0.01, P<0.05), but serum GH content showed no different between isinglass prevention group and model group. CONCLUSION: Isinglass preventes the gastric mucosal atrophy in the CAG model. Its mechanism may be related to the effects of decreasing the gastric mucosal damage， promoting the cell proliferation and increasing of internal EFG secretion.     

Effects of DEHP on testosterone synthesis in fetal Leydig cells of newborn male rats

AIM: To observe the effects of diethylhexylphthalate(DEHP) on testosterone synthesis in fetal Leydig cells(FLC) of newborn male rats.METHODS: The pregnant rats were exposed to DEHP at dose of 10 mg·kg^-1·d^-1, 100 mg·kg^-1·d^-1 or 750 mg·kg^-1·d^-1(body weight) by gavage from gestation 12 days(GD 12) to postnatal 1 day(PND 1) respectively. The serum level of testosterone was detected by chemiluminescence. The morphology of FLC from the testes was observed under light microscope and transmission electron microscope. The mRNA expression of steroidogenic acute regulatory protein(StAR) and insulin-like growth factor I(IGF-I) was detected by real-time PCR(ΔΔCT). RESULTS: The serum testosterone level in low dose group was significantly higher than that in control, middle and high dose groups. The serum testosterone level in middle and high dose groups was significantly lower than that in control group(P<0.05). Light microscopy showed the aggregative cluster distribution of FLCs in low dose group, while manifested as tumor-like hyperplasia of FLCs in middile dose group and high dose group. Under electron microscope, the FLC in low dose group showed oval-shape or long spindle-shape, the lipid particles were decreased, but smooth endoplasmic reticulum and mitochondria were increased in cytoplasm. In middle and high dose group, the FLC were spindle or oval-shaped, showed large or small, nuclear large, round, rich in cytoplasm and cell aggregation, the cytoplasm was rich lipid particles with deep-stained, smooth endoplasmic reticulum and mitochondria were expanded. Compared to control group, the mRNA expression of StAR in low, middle and high dose group was decreased. The mRNA expression of StAR in high dose group was decreased more significantly(P<0.01) as compared to that in control group, while the mRNA expression of IGF-I in low dose group and middle dose group was increased, but that only in low dose group was increased more significantly as compared to control group(P<0.01). CONCLUSION: DEHP has toxic effect on FLC and changes the morphology and steroidogenic capacity in testicular FLC. The low dose of DEHP elevates the gene expression of IGF-I, and IGF-I stimulates the production of testosterone by FLC. The high dose of DEHP may inhibit the gene expression of StAR to reduce the serum levels of testosterone.     

Antidepressant effect of dextromethorphan and its mechanism

AIM:To investigate the antidepressant effect of dextromethorphan (DXM) and its mechanism. METHODS:The antidepressant effect of DXM was observed by the methods of forced swimming test, tail suspension test and open field test. The N-methyl-D-aspartate (NMDA) receptor activity in brain, and the effects of total nitric oxide synthases (NOS) and various types of NOS were examined by molecular biology methods. The mice pretreated with NMDA receptor antagonist MK-801 (MK), NMDA, NO precursor L-arginine (L-ARG), endothelial NOS (eNOS) inhibitor N^ω-nitro-L-arginine methyl ester (L-NAME), inducible NOS (iNOS) inhibitor aminoguanidine (AG), neuronal NOS (nNOS) inhibitor 7-nitroindole (7-NI) or phosphodiesterase 5 inhibitor sildenafil were given DXM to explore the mechanism of DXM as an antidepressant. RESULTS:DXM had a dose-dependent antidepressant effect. DXM inhibited the activity of brain NMDA receptor in a dose-dependent manner, and inhibited the expression of eNOS and nNOS. MK, L-NAME and 7-NI were able to promote the antidepressant effect of DXM. NMDA, L-ARG and sildenafil were able to inhibit the antidepressant effect of DXM. AG did not influence the antidepressant effect of DXM. CONCLUSION:DXM has an antidepressant effect, and NMDA receptor and L-ARG-NO-cGMP signaling pathways are involved in this process.     

Effect of andrographolide on osteosarcoma 143B cells and its mechanism

AIM To investigate the inhibitory effect of andrographolide （AG） on human osteosarcoma 143B cells and its underlying molecular mechanism. METHODS Osteosarcoma 143B cells were cultured in vitro and treated with AG at different concentrations (0~20 μmol/L), and the effect of AG on the proliferation of 143B cells was determined by crystal violet staining, MTT assay and colony formation assay. The wound-healing assay was performed to detect the migration ability of osteosarcoma 143B cells. Transwell assay was performed to analyze the invasive capacity of osteosarcoma 143B cells. The effect of AG on the apoptosis of osteosarcoma 143B cells was detected by Hoechst 33258 staining and flow cytometry. After treatment with of AG at different concentrations, the protein levels of the molecules related to proliferation, migration, invasion and apoptosis of osteosarcoma 143B cells were determined by Western blot. The expression of β-catenin and its related molecule c-Myc in the Wnt signaling pathway was analyzed by Western blot. RESULTS Compared with blank group, the proliferation, migration and invasion of osteosarcoma 143B cells in AG treatment group were significantly inhibited (P<0.05) in a concentration-dependent manner. The expression levels of invasion- and migration-related proteins matrix metalloproteinase-9 (MMP-9), vimentin and Snail were all down-regulated (P<0.05). AG also increased the expression of antiapoptotic protein Bcl-2, and the levels of apoptosis-related protein caspase-3 was decreased but cleaved caspase-3 was increased. At the same time, the expression levels of Wnt/β-catenin signaling pathway related proteins β-catenin and c-Myc were significantly decreased (P<0.05). CONCLUSION Andrographolide may inhibit the proliferation, migration, and invasion of osteosarcoma 143B cells and promote their apoptosis by inhibiting the activity of Wnt signaling pathway.     

Damaging effects of exogenous spermine on HUVECs and its possible mechanism

AIM: To study the effects of exogenous spermine on human umbilical veins endotheliocytes (HUVECs) and to explore its possible mechanism. METHODS: The serial subculture of HUVECs was used to investigate the effect of exogenous spermine with different concentrations (50 μmol/L-5 mmol/L) on HUVECs in different times (2 h, 4 h). The morphological changes of HUVECs (by inverted microscope and electron microscope), the cell viability, the level of MDA and activity of SOD were observed. RESULTS: Compared to normal control group, no change of all index detected in the group with spermine (50 μmol/L) was observed (P>0.05). Spermine injured HUVECs in a concentration-dependent manner. After adding spermine for 2 h and 4 h, it was observed that cellular injury in 4 h group was more serious than that in 2 h group. The injury of HUVECs caused by exogenous spermine was characterized by decrease in cellular viability and activity of SOD, ultrastructural injury, increase in MDA level. CONCLUSION: Exogenous spermine induces the injury of HUVECs in concentration and time-dependent manners. Its mechanisms may be related to lipid peroxidation induced by increase in the production of oxygen free radical.     

Effects of testosterone on endothelial function and intimal proliferation after balloon injury in male rabbit abdominal aorta

AIM: To investigate the effects of testosterone on endothelial function and intimal proliferation after balloon injury in male rabbit abdominal aorta. METHODS: 24 male New Zealand white rabbits were divided randomly into three groups: control group (n=8, sham castration), hypotestosteronemia group (n=8,castration) and testosterone replacement group (n=8,castration +testosterone undecanoate intramuscular injection,14mg/kg). Abdominal aorta was injured with 3 mm PTCA balloon after testosterone undecanoate had been injected for three days. Two weeks later, blood samples were obtained for detection of plasma testosterone, lipids, metabolic product of nitric oxide (NO₂^-／NO₃^-), superoxide dismutase(SOD) and malondialdehyde (MDA),and all the abdominal aorta were excised to be analyzed by computer. RESULTS: The intimal area of hypotestosteronemia group were significantly larger than that of other two groups(P＜0.01). plasma NO₂^-／NO₃^- and SOD levels were significantly decreased, while the total cholesterol(TC),triglycerides(TG), low density lipoprotein(LDL) and plasma MDA were significantly increased. No difference was observed between control group and testosterone replacement group in all parameters. CONCLUSION: Testosterone, at physiological level,had the effects of inhibiting the intimal proliferation and of protecting the endothelial function after balloon injury in male rabbit abdominal aorta.     

Role of the coagulation and fibrinolysis in acute lung injury

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common, life-threatening causes of acute respiratory failure that arise from a variety of local and systemic insults. The pathogenesis of ALI/ARDS is complicated and not yet completely interpreted today. The role of altered coagulation and fibrinolysis in the pathogenesis of ALI/ARDS has been investigated. This review will summarize the current understanding of coagulation and fibrinolysis in human ALI/ARDS with emphasis on pathways that could be potential therapeutic targets. These pathways include the tissue factor pathway, the protein C pathway and modulation of fibrinolysis via plasminogen activator inhibitor-1.