Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chronological expression (over 24 h) of two adhesion molecules [intercellular adhesion molecule-1 (ICAM-1) and CD11b/CD18 (Mac-1)] and the extent of liver damage, including injury to sinusoidal endothelial cells (SECs) and hepatocyte apoptosis, were investigated under two conditions of rat liver ischemia-reperfusion (I/R) injury: reversible (30 min) and fatal I/R (60 min). The chronological profiles of upregulation of ICAM-1 on hepatocytes and Mac-1 showed changes in parallel with the other liver damage parameters, and the extent of upregulation and various parameters of liver injury were more advanced in the 60-min I/R group. Paradoxically, the degree of ICAM-1 upregulation of SECs decreased significantly in the 60-min I/R group vs. the 30-min I/R group. Repression of hepatocyte apoptosis by administration of the caspase inhibitor ZVAD-fmk resulted in attenuation of neutrophil infiltration and liver injury. These findings indicate that 1) neutrophil infiltration is involved in the development of liver I/R injury; 2) interaction between ICAM-1 on SECs and Mac-1 on neutrophils is not an essential step for neutrophil transmigration through the endothelial layer because SECs, specifically, were impaired in the early stages of liver I/R injury; 3) the role of ICAM-1 and Mac-1 is to adhere neutrophils firmly to hepatocytes and activate neutrophils; and 4) excessive parenchymal apoptosis may be the signal for the neutrophil-induced inflammatory and necrotic reaction.
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PMID:Mac-1 (CD11b/CD18) and intercellular adhesion molecule-1 in ischemia-reperfusion injury of rat liver. 1144 39

Microglia are a major glial component of the central nervous system (CNS), play a critical role as resident immunocompetent and phagocytic cells in the CNS, and serve as scavenger cells in the event of infection, inflammation, trauma, ischemia, and neurodegeneration in the CNS. Studies of human microglia have been hampered by the difficulty of obtaining sufficient numbers of human microglia. One way to circumvent this difficulty is to establish permanent cell lines of human microglia. In the present study we report the generation of immortalized human microglial cell line, HMO6, from human embryonic telencephalon tissue using a retroviral vector encoding myc oncogene. The HMO6 cells exhibited cell type-specific antigens for microglia-macrophage lineage cells including CD11b (Mac-1), CD68, CD86 (B7-2), HLA-ABC, HLA-DR, and ricinus communis agglutinin lectin-1 (RCA), and actively phagocytosed latex beads. In addition, HMO6 cells showed ATP-induced responses similar to human primary microglia in Ca2+ influx spectroscopy. Both human primary microglia and HMO6 cells showed the similar cytokine gene expression in IL-1beta, IL-6, IL-8, IL-10, IL-12, IL-15, and TNF-alpha. Using HMO6 cells, we investigated whether activation was induced by Amyloid-beta fragments or lipopolysaccharide (LPS). Treatment of HMO6 cells with Amyloid-beta 25-35 fragment (Abeta(25-35)) or Amyloid-beta 1-42 fragment (Abeta(1-42)) led to increased expression of mRNA levels of cytokine/chemokine IL-8, IL-10, IL-12, MIP-1beta MIP-1, and MCP-1, and treatment with LPS produced same results. Expression of TNF-alpha and MIP1-alpha was not detected in unstimulated HMO6 cells, but their expression was later induced by long-term exposure to Abeta(25-35) or Abeta(1-42.) ELISA assays of spent culture media showed increased protein levels of TNF-alpha and IL-8 in HMO6 cells following treatment with Abeta(25-35) or LPS. Taken together, our results demonstrate that treatment of human primary microglia and HMO6 immortalized human microglia cell line with Abeta(25-35), Abeta(1-42) and LPS upregulate gene expression and protein production of proinflammatory cytokines and chemokines in these cells. The human microglial cell line HMO6 exhibits similar properties to those documented in human microglia and should have considerable utility as an in vitro model for the studies of human microglia in health and disease.
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PMID:Generation and characterization of immortalized human microglial cell lines: expression of cytokines and chemokines. 1174 1

The diabetic vasculopathy is one of the major complications responsible for the high incidence of arteriopathy, coronary ischemia and renal failure. Several hypothesis have been formulated to explain the vascular abnormalities. We recently showed that advanced glycation end products (AGE) have a pivotal role in the genesis of vascular dysfunction. AGE bind to a receptor (RAGE) present on endothelial cells. AGE binding to RAGE produced an oxidant stress and diminished vascular barrier function, increased vascular permeability, enhanced the expression of vascular cell adhesion molecule 1 (VCAM-1). VCAM-1 expression on endothelial cell and increased expression of CD11b CD18 on monocytes may facilitate monocyte emigration and can represent one of the initial steps of vascular alteration. In diabetic animals or in ApoE null diabetic mice which developed atherosclerosis, the infusion of recombinant RAGE prepared in insect cells was studied. Recombinant RAGE administration corrected vascular hyperpermeability and prevented the development of atherosclerosis in the animals.
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PMID:Blood cells and vascular cell interactions in diabetes. 1179 Aug 70

Highly elevated partial pressures of oxygen achievable during hyperbaric oxygenation (HBO) have been shown to reduce leukocyte sequestration following ischemia/reperfusion injury suggesting a clinical role for HBO in treatment of various disease states characterized by transient ischemia. Previous studies have suggested that this effect may be due to inhibition of beta2-integrin function. In this study the effect of HBO on various CD11b/CD18 (Mac-1) mediated neutrophil functions was investigated in healthy human subjects. HBO 3.0 ATA, 23 m reduced adhesion 50% at 2 h with return to pre-HBO levels by 6 h. Homotypic aggregation, a Mac-1 dependent function, under fluid shear following stimulation with f-MLP was reduced from 20+/-2.6 to 3.4+/-1.0% 2 h after HBO. However, HBO did not inhibit adhesion to IL-1beta stimulated HUVEC. Mac-1 mediated oxidative burst induced by opsonized zymosan was reduced 38.2+/-10.6% (P<0.05) by HBO. However, oxidative burst induced by PMA or f-MLP was not affected. HBO did not alter the distribution of neutrophils displaying morphologies associated with stimulation (ruffled, bipolar, uropod) over a 24 h period after HBO nor did HBO change the percentages of mature versus immature cells. Taken together these findings demonstrate that HBO specifically inhibits Mac-1 mediated functions.
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PMID:Hyperbaric oxygen exposure temporarily reduces Mac-1 mediated functions of human neutrophils. 1206 61

In this study, we adapted the original rat photothrombosis model of Watson et al. (Ann Neurol 17 (1985) 497) for use in mice by refining the application route of the dye, illumination and stereotactic parameters. After intraperitoneal injection of the photosensitive dye Rose bengal, subsequent focal illumination of the brain with a cold light source through the intact skull led to focal cortical infarcts of reproducible size, location and geometry. Cresyl violet histology displayed well-demarcated infarcts that matured with time in a predictable manner. Microglial responses, as assessed by immunocytochemistry, against F4/80 and CD11b antigens were rapid and complete at the infarct site, but delayed and incomplete in degenerating fiber tracts and ipsilateral thalamic nuclei. In contrast to the rat, where the expression of CD4 and CD8 antigens discriminate distinct subpopulations of lesion-associated phagocytes, the expression of both markers was low to absent in the mouse model. In both rats and mice, cerebral photothrombosis shares essential inflammatory responses with focal ischemia induced by middle cerebral artery occlusion. It may provide a useful model to study functional aspects of lesion-associated and remote molecular responses in transgenic mice.
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PMID:Non-invasive induction of focal cerebral ischemia in mice by photothrombosis of cortical microvessels: characterization of inflammatory responses. 1208 63

Lack of enteral feeding increases P- and E-selectin and ICAM-1 expression on endothelial cells in organs, such as the small intestine and lung, and increases neutrophils in the intestine. These changes are associated with increased mortality after gut ischemia. We hypothesize that nutritional regimen affects endothelial ICAM-1 levels and leukocyte beta2 integrins after gut ischemia. Mice received chow, intravenous (IV) TPN, or intragastric (IG) TPN. In experiment 1, after 5 days of diet, 28 mice underwent 15 min of superior mesenteric artery (SMA) occlusion (I/R) for quantification of ICAM-1 expression in organs 3 h later. In experiment 2, after the same nutrient pretreatments of 38 mice, peripheral blood was obtained with or without gut I/R to measure CD11a and CD11b expression on myeloid cells. CD18 immunofluorescence staining was studied in the lung. Expression of ICAM-1 in the liver, kidney, and small intestine was significantly higher after IV-TPN than chow. IG-TPN reduced liver and kidney ICAM-1 levels midway between the chow and IV-TPN groups, but not intestinal expression. Expression of CD11b on the myeloid cell population in each group was similar before I/R, but CD11b levels increased after IV-TPN on circulating cells after I/R compared with all uninjured animals or injured chow or IG-TPN mice. Only IV-TPN mice had lung CD18-positive leukocytes after I/R. After I/R, lack of enteral feeding increases organ expression of ICAM-1, CD11b levels on myeloid cells, and lung of CD18 positive leukocytes. Through these changes, lack of enteral feeding may increase organ damage after gut ischemia.
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PMID:Increased ICAM-1 and beta2 integrin expression in parenterally fed mice after a gut ischemic insult. 1216 73

Neutrophil adhesion to coronary endothelium is a key event for cardiac reperfusion injury. Adhesion is proposed to be a multi-step event, consisting of selectin-mediated rolling, chemotactic activation, and subsequent integrin-mediated firm attachment. However, it is not clear whether this sequence also occurs in the coronary circulation with its unique hemodynamic properties (turbulent flow, flow reversal). We have studied neutrophil adhesion in the coronary system of isolated perfused guinea pig hearts under basal and reperfusion conditions (15 min global ischemia). Adhesion was manipulated by an anti-CD18 antibody (blocking firm adhesion) and fucoidin (reducing rolling). Neutrophil behavior during coronary passage was assessed by measurement of CD11b expression, forward scatter (FSC, indicating polarization), and sideward scatter (SSC, measure for granularity) via flow cytometry. Adhesion rose from 21 % (basal) to 35 % after ischemia. Anti-CD18 decreased adhesion to 11 % and 14 %, respectively; fucoidin altered only the postischemic increase (23 %). CD11b was unchanged by passage through the non-ischemic coronaries, but rose postischemically (139 % increase). CD18 blockade did not reduce the postischemic rise of CD11b, while fucoidin was inhibitory (24 % increase). FSC did not differ between controls and ischemic hearts in any group, while SSC decreased most in postischemic hearts after CD18 blockade. Blockade of rolling and of firm attachment both reduce neutrophil retention, while only inhibition of rolling reduces intracoronary activation. Thus, rolling seems to be mandatory for endothelial-leukocyte communication in the coronary system.
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PMID:Selectin-mediated rolling of neutrophils is essential for their activation and retention in the reperfused coronary system. 1220 Jun 35

Amputated tissue maintained in a hypothermic environment can endure prolonged ischemia and improve replantation success. The authors hypothesized that local tissue hypothermia during the early reperfusion period may provide a protective effect against ischemia-reperfusion injury similar to that seen when hypothermia is provided during the ischemic period. A rat gracilis muscle flap model was used to assess the protective effects of exposing skeletal muscle to local hypothermia during ischemia only (p = 18), reperfusion only (p = 18), and both ischemia and reperfusion (p = 18). Gracilis muscles were isolated and exposed to hypothermia of 10 degrees C during 4 hours of ischemia, the initial 3 hours of reperfusion, or both periods. Ischemia-reperfusion outcome measures used to evaluate muscle flap injury included muscle viability (percent nitroblue tetrazolium staining), local edema (wet-to-dry weight ratio), neutrophil infiltration (intramuscular neutrophil density per high-power field), neutrophil integrin expression (CD11b mean fluorescence intensity), and neutrophil oxidative potential (dihydro-rhodamine oxidation mean fluorescence intensity) after 24 hours of reperfusion. Nitroblue tetrazolium staining demonstrated improved muscle viability in the experimental groups (ischemia-only: 78.8 +/- 3.5 percent, p < 0.001; reperfusion-only: 80.2 +/- 5.2 percent, p < 0.001; and ischemia-reperfusion: 79.6 +/- 7.6 percent, p < 0.001) when compared with the nonhypothermic control group (50.7 +/- 9.3 percent). The experimental groups demonstrated decreased local muscle edema (4.09 +/- 0.30, 4.10 +/- 0.19, and 4.04 +/- 0.31 wet-to-dry weight ratios, respectively) when compared with the nonhypothermic control group (5.24 +/- 0.31 wet-to-dry weight ratio; p < 0.001, p < 0.001, and p < 0.001, respectively). CD11b expression was significantly decreased in the reperfusion-only (32.65 +/- 8.75 mean fluorescence intensity, p < 0.001) and ischemia-reperfusion groups (25.26 +/- 5.32, p < 0.001) compared with the nonhypothermic control group (62.69 +/- 16.93). There was not a significant decrease in neutrophil CD11b expression in the ischemia-only group (50.72 +/- 11.7 mean fluorescence intensity, p = 0.281). Neutrophil infiltration was significantly decreased in the reperfusion-only (20 +/- 11 counts per high-power field, p = 0.025) and ischemia-reperfusion groups (23 +/- 3 counts, p = 0.041) compared with the nonhypothermic control group (51 +/- 28 counts). No decrease in neutrophil density was observed in the ischemia-only group (40 +/- 15 counts per high-power field, p = 0.672) when compared with the nonhypothermic control group (51 +/- 28 counts). Finally, dihydrorhodamine oxidation was significantly decreased in the reperfusion-only group (45.83 +/- 11.89 mean fluorescence intensity, p = 0.021) and ischemia-reperfusion group (44.30 +/- 11.80, p = 0.018) when compared with the nonhypothermic control group (71.74 +/- 20.83), whereas no decrease in dihydrorhodamine oxidation was observed in the ischemia-only group (65.93 +/- 10.3, p = 0.982). The findings suggest a protective effect of local hypothermia during early reperfusion to skeletal muscle after an ischemic insult. Inhibition of CD11b expression and subsequent neutrophil infiltration and depression of neutrophil oxidative potential may represent independent protective mechanisms isolated to local tissue hypothermia during the early reperfusion period (reperfusion-only and ischemia-reperfusion groups). This study provides evidence for the potential clinical utility of administering local hypothermia to ischemic muscle tissue during the early reperfusion period.
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PMID:Local hypothermia during early reperfusion protects skeletal muscle from ischemia-reperfusion injury. 1249 85

The hepatic reticuloendothelial system (RES) is the primary mechanism for removing circulating bacteria from the systemic circulation. While Kupffer cells are important for this process, leukocytes appear to play a significant role as well. Hepatic leukocyte accumulation following ischemia/reperfusion or cytokine stimulation is well documented, but its contribution to phagocytic killing by the hepatic RES is not fully understood. We evaluated the role of leukocytes in general, and leukocyte-endothelial adhesion in particular, in hepatic RES function. This was done by inducing confirmed leukopenia with cyclophosphamide or by blocking leukocyte-endothelial adhesion molecules with specific blocking antibodies. Hepatic phagocytic clearance (HPC) and hepatic phagocytic killing (HKE) of systemically intravenously injected E. coli were assayed and quantitated by a validated dual isotope label technique. HPC among the various experimental groups and respective controls varied only slightly, with no statistically significant differences observed. Leukopenia or CD11b blockade each significantly decreased the HKE relative to the controls. Antibody blockade of certain other adhesion molecules had no significant effect on HKE (or HPC). The role of leukocytes in killing systemically circulating bacteria is an integral component of hepatic RES function. This capability of the leukocyte appears to be dependent, in part, on the adhesion molecule, Mac-1.
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PMID:Hepatic killing but not clearance of systemically circulating bacteria is dependent upon peripheral leukocytes via Mac-1 (CD11b/CD18). 1263 May 27

Free tissue transfers and replantation of amputated limbs are better tolerated by young adolescents than mature adults. The authors hypothesized that this observation may be, in part, because of an attenuated ischemia-reperfusion (IR) injury in younger patients. Because neutrophils have been identified as a critical cell line responsible for IR injury, the authors investigated the effects of animal age on the degree of neutrophil activation in a rat model. Activation was evaluated by monitoring expression of integrin surface markers (mean fluorescence intensity [MFI] of CD11b) and oxidative burst potential (MFI of dihydrorhodamine [DHR] oxidation) by flow cytometry in neutrophils analyzed after 4 hours of ischemia and 1, 4, and 16 hours of reperfusion in a gracilis muscle flap model in mature adult and young adolescent rats. Neutrophil activation was also evaluated in control sham-operated animals, which underwent elevation of gracilis muscle flaps without exposure to an ischemic insult. Muscle edema, determined by wet-to-dry muscle weight ratio, and muscle viability, determined by nitro blue tetrazolium (NBT) staining, were completed for gracilis muscles exposed to ischemia after 24 hours of reperfusion for each of the groups. Integrin expression, assessed by MFI of CD11b, was increased significantly in ischemic muscles of mature adult rats at 4 hours of reperfusion (71.10+/-3.53 MFI vs. 54.88+/-12.73 MFI, p=0.025). Neutrophil oxidative potential, assessed by MFI of DHR oxidation, was increased significantly in ischemic muscles of mature adult rats compared with young adolescent rats at 1 hour of reperfusion (78.10+/-9.53 MFI vs. 51.78+/-16.91 MFI, p=0.035) and 4 hours of reperfusion (83.69+/-15.29 MFI vs. 46.55+/-8.09 MFI, p=0.005). Increased edema formation was observed in the ischemic muscles of mature adult rats when compared with young adolescent rats (1.25+/-0.04 vs. 1.12+/-0.05, p=0.031) after 24 hours of reperfusion. A trend toward decreased muscle viability was observed in the mature adult rats when compared with young adolescent rats (23.7+/-3.1% NBT staining vs. 32.3+/-13.7% NBT staining, p=0.189) after 24 hours of reperfusion. The authors present evidence of an attenuated IR injury in young adolescent animals when compared with mature adult rats. These findings emphasize the importance that studies involving IR injury should be performed with consideration of animal age.
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PMID:Age-related differences of neutrophil activation in a skeletal muscle ischemia-reperfusion model. 1267 84


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