Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The aim of our study was to investigate the effects of recombinant human granulocyte-colony stimulating factor in a rat model of splanchnic ischaemia-reperfusion injury. 2. Male anaesthetized rats were subjected to clamping of the splanchnic arteries for 45 min. This surgical procedure resulted in an irreversible state of shock (splanchnic artery occlusion shock. SAO shock). Sham operated animals were used as controls. Survival rate, serum tumour necrosis factor-alpha (TNF-alpha), neutrophil count, bone marrow myeloid precursor cells, myeloperoxidase activity (MPO; studied as a quantitative means to assess leukocyte accumulation), mean arterial blood pressure and the responsiveness of aortic rings to phenylephrine (PE, 1 nM-10 microM) were studied. 3. SAO shocked rats had a decreased survival rate (0% at 4 h of reperfusion, while sham shocked rats survived more than 4 h), increased serum levels of TNF-alpha (201 +/- 10 u ml-1; sham shocked rats = undetectable), neutropenia, enhanced MPO activity in the ileum (0.11 +/- 0.06 u x 10(-3) g-1 tissue; sham shocked rats = 0.02 +/- 0.001 u x 10(-3) g-1 tissue) and in the lung (1.5 +/- 0.2 u x 10(-3) g-1 tissue; sham shocked rats = 0.19 +/- 0.05 u x 10(-3) g-1 tissue) and unchanged bone marrow myeloid precursor cells. Furthermore aortic rings from shocked rats showed a marked hyporeactivity to PE. 4. Administration of recombinant human granulocyte colony stimulating factor (rh G-CSF; 5, 10 and 20 micrograms kg-1 5 min following the release of occlusion) increased in a dose-dependent manner survival rate (90% at 4 h of reperfusion with the dose of 20 u x 10(-3) g kg-1), reduced serum TNF-alpha (13 +/- 5 u ml-1) and MPO activity in the ileum (0.065 +/- 0.002 u x 10(-3) g-1 tissue) and in the lung (0.7 +/- 0.03 microgram kg-1 tissue), improved neutropenia and mean arterial blood pressure but did not modify bone marrow myeloid progenitor cells. Furthermore rh G-CSF, either in vivo or in vitro (200 nM for 1 h in the organ bath), restored to control values the hyporeactivity to PE. Finally rh G-CSF potently inhibited the activity of inducible nitric oxide synthase in peritoneal macrophages activated with endotoxin. 5. Our results suggest that rh G-CSF protects against splanchnic ischaemia reperfusion injury by a mechanism(s) that does not depend upon its haematopoietic effects.
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PMID:The effects of recombinant human granulocyte-colony stimulating factor on vascular dysfunction and splanchnic ischaemia-reperfusion injury. 911 28

Studies were conducted with rats to investigate whether exposure to carbon monoxide (CO) at concentrations frequently found in the environment caused lung injury mediated by nitric oxide (*NO)-derived oxidants. Lung capillary leakage was significantly increased 18 h after rats had been exposed to CO at concentrations of 50 ppm or more for 1 h. An elevation of *NO during CO exposure was demonstrated by electron paramagnetic resonance spectroscopy. There was a 2.6-fold increase of *NO over control in the lungs of rats exposed to 100 ppm CO. A qualitative increase in the concentration of H2O2 was also detected in lungs during CO exposure, and this change was caused by *NO as it was inhibited in rats pretreated with the nitric oxide synthase inhibitor, Nomega nitro-l-arginine methyl ester (l-NAME). Production of *NO-derived oxidants during CO exposure was indicated by an elevated concentration of nitrotyrosine in lung homogenates. The CO-associated elevations in lung capillary leakage and nitrotyrosine concentration did not occur when rats were pretreated with l-NAME. CO exposure did not change the concentrations of endothelial or inducible nitric oxide synthase in lung and leukocyte sequestration was not detected as a consequence of CO exposure. CO-mediated lung leak and nitrotyrosine elevation were not affected by neutropenia. We conclude that CO exposure elevates the steady-state concentration of *NO in lungs. Consequences from this change include increases in the concentration of reactive oxygen species, production of *NO-derived oxidants such as peroxynitrite, and physiological evidence of lung injury.
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PMID:Pulmonary vascular stress from carbon monoxide. 988 87

Polymorphonuclear leukocytes (PMN) and inducible nitric oxide synthase (iNOS) appear to play important roles in the liver and in lung injury induced by hemorrhagic shock. Their precise roles in hemorrhagic shock-induced acute gastric mucosal lesions (AGML), however, are still poorly understood. In this study, we investigated the effect of neutropenia on hemorrhagic shock-induced AGML. We also examined the roles of iNOS in PMN infiltration into the mucosa and AGML during hemorrhagic shock by using L-N6-(1-iminoethyl)-lysine, a potent inhibitor of iNOS, and by reverse transcriptase polymerase chain reaction. Remarkable gastric mucosal damage occurs after hemorrhagic shock. PMN depletion caused by Vinblastine pretreatment significantly attenuates this AGML. Although low-dose L-N6-(1-iminoethyl)-lysine (50 microg/kg, iNOS inhibition) has no effect on AGML, high-dose L-N6-(1-iminoethyl)-lysine (250 microg/kg, iNOS + endothelial NOS inhibition) significantly exacerbates AGML without increasing PMN infiltration into the mucosa. The mRNA expression of iNOS in the stomach during hemorrhagic shock cannot be detected by reverse transcriptase polymerase chain reaction. We conclude that PMN play a pivotal role in hemorrhagic shock-induced AGML, iNOS does not regulate PMN infiltration into the mucosa, and endothelial NOS provides important protection against AGML during hemorrhagic shock.
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PMID:Neutrophil accumulation and damage to the gastric mucosa in resuscitated hemorrhagic shock is independent of inducible nitric oxide synthase. 1035 36

Evidence showing that neutrophils play a protective role in the host response to infection by different intracellular parasites has been published in the past few years. We assessed this issue with regard to the infection of mice with Mycobacterium tuberculosis. We found a chronic recruitment of neutrophils to the infection foci, namely, to the peritoneal cavity after intraperitoneal infection and to the spleen and liver after intravenous inoculation of the mycobacteria. However, bacilli were never found associated with the recruited neutrophils but rather were found inside macrophages. The intravenous administration of the antineutrophil monoclonal antibody RB6-8C5 during the first week of infection led to selective and severe neutropenia associated with an enhancement of bacillary growth in the target organs of the mice infected by the intravenous route. The neutropenia-associated exacerbation of infection was most important in the liver, where a bacterial load 10-fold higher than that in nonneutropenic mice was found; the exacerbation in the liver occurred both during and after the neutropenic period. Early in infection by M. tuberculosis, neutropenic mice expressed lower levels of mRNAs for gamma interferon and inducible nitric oxide synthase in the liver compared to nondepleted mice. These results point to a protective role of neutrophils in the host defense mechanisms against M. tuberculosis, which occurs early in the infection and is not associated with the phagocytic activity of neutrophils but may be of an immunomodulatory nature.
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PMID:Neutrophils play a protective nonphagocytic role in systemic Mycobacterium tuberculosis infection of mice. 1063 20

Whether leukocytes exert an influence on vascular function in vivo is not known. Here, genetic and pharmacologic approaches show that the absence of neutrophils leads to acute blood pressure dysregulation. Following neutrophil depletion, systolic blood pressure falls significantly over 3 days (88.0 +/- 3.5 vs 104.0 +/- 2.8 mm Hg, day 3 vs day 0, mean +/- SEM, P < .001), and aortic rings from neutropenic mice do not constrict properly. The constriction defect is corrected using l-nitroarginine-methyl ester (L-NAME) or the specific inducible nitric oxide synthase (iNOS) inhibitor 1400W, while acetylcholine relaxation is normal. iNOS- or IFNgamma-deficient mice are protected from neutropenia-induced hypotension, indicating that iNOS-derived nitric oxide (NO) is responsible and that its induction involves IFNgamma. Oral enrofloxacin partially inhibited hypotension, implicating bacterial products. Roles for cyclooxygenase, complement C5, or endotoxin were excluded, although urinary prostacyclin metabolites were elevated. Neutrophil depletion required complement opsinization, with no evidence for intravascular degranulation. In summary, circulating neutrophils contribute to maintaining physiological tone in the vasculature, at least in part through suppressing early proinflammatory effects of infection. The speed with which hypotension developed provides insight into early changes that occur in the absence of neutrophils and illustrates the importance of constant surveillance of mucosal sites by granulocytes in healthy mice.
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PMID:Circulating neutrophils maintain physiological blood pressure by suppressing bacteria and IFNgamma-dependent iNOS expression in the vasculature of healthy mice. 1846 8