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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Granulocyte (PMN)-endothelial interactions have been implicated in the primary events of vascular injury and atherogenesis. We now present data which show that endogenous opioid peptides, e.g. enkephalins (ENK), dampen immune-triggered, granulocyte-induced endothelial damage by enhancing prostacyclin production. Concurrent exposure of human umbilical vein endothelial cells (HUEC) to Met5-enkephalin increased arachidonic acid (AA, 20 muM) and thrombin (T, 10 U/ml) induced 6-keto-PGF1 alpha-release to respectively 197.2 +/- 28.1% and 204.1 +/- 17.8% (mean +/- SEM) of base line stimulation (p less than 0.025). The increases noted were significant at ENK-concentrations as low as 10(-12)M. Simultaneous addition of naloxone with ENK completely abolished the enhanced 6-keto-PGF1 alpha-release. Addition of a protease resistant enkephalin analogue significantly (p less than 0.01 over several different concentrations) reduced PMN adherence to HUEC; concomitantly 51Cr-leakage from HUEC that had been exposed to PMN plus activated serum complement was decreased. The even further enhanced 51Cr-leakage that occurs when platelet release products (e.g. serotonin) are included is also decreased by added enkephalin. These data suggest that endogenous neurotransmitters may affect endothelial prostaglandin metabolism, and by so doing provide a protective effect during in vitro, and perhaps in vivo, PMN mediated endothelial injury. This link between neurohumoral and inflammatory systems might enhance our understanding of stress-related phenomena in inflammation and vascular diseases.
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PMID:Enkephalins modify granulocyte-endothelial interactions by stimulating prostacyclin production. 635 55

A prospective study of 10 patients undergoing hemodialysis showed that less neutropenia and complement activation occurred with dialyzer reuse. Neutrophil counts fell 95% +/- 5% (SEM) with first use and 66% +/- 8% and 48% +/- 10% with second and third uses, respectively (p less than 0.05). The production of complement component C5a-desarg, as measured by the bioassay granulocyte aggregation, was decreased by 96% +/- 1% and 93% +/- 2% with second and third uses, respectively (p less than 0.05). We investigated the role of the dialyzer disinfectant formaldehyde in decreased neutropenia. In vitro, formaldehyde inhibited granulocyte aggregation and chemotaxis and the dialyzer membrane's ability to generate granulocyte aggregating activity; however, this occurred only at concentrations higher than those likely to obtain in patients. The ability of dialysis membranes to generate granulocyte aggregating activity in plasma was decreased 55% +/- 5% by their prior sequential preincubation in plasma and then formalin (p less than 0.05) and extensive rinsing, which is similar to the circumstances obtaining with dialyzer reuse. Preincubation of membranes in plasma or formalin alone resulted in no change in the membrane's ability to generate granulocyte aggregating activity. We conclude that the exposure of membranes to both plasma and formalin during dialysis and storage is responsible for the decreased C5a-desarg production with reuse, probably because plasma proteins are fixed to the membrane in such a way that interrupts free interaction between the membrane and plasma complement components.
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PMID:Effect of dialyzer reuse on complement activation and neutropenia in hemodialysis. 647 May 61

The number of committed granulocyte-monocyte precursors (CFU-GM) in circulation has been shown to increase following steroid administration in humans. To see if steroids could be used to improve the collection of peripheral blood stem cells for haematopoietic reconstitution, their effect on circulating CFU-GEMM was investigated. Six healthy young adults, three men and three women, were given 60 mg of prednisone orally at 8 a.m. on day 1. Blood CFU-GEMM and committed precursors (CFU-GM and BFU-E) were cultured in methylcellulose. Samples were taken at 4 p.m. the day before and at 8 a.m. on the day of steroid administration, and at 4, 8, 24 and, in a few cases, 48 h after steroid. Pre-treatment CFU-GEMM levels (per unit volume of blood) at 4 p.m. was 180 +/- 23% (mean +/- SEM) of that at 8 a.m., showing a significant (P less than 0.025) diurnal variation. 8 h after steroids there was a fall in CFU-GEMM to 28 +/- 4.5% of the 8 a.m. presteroid level. 24 h following steroid administration, CFU-GEMM rose significantly (P less than 0.05) to 188 +/- 33% of 8 a.m. baseline values; CFU-GM and BFU-E changes generally paralleled those noted for CFU-GEMM. These results suggest that blood levels of CFU-GEMM exhibit a significant diurnal variation. Oral prednisone given 24 h in advance of collection increases the 8 a.m. value to that found at 4 p.m. The steroid effect may be due to a resetting of the diurnal control mechanism. Use of this information may be important in collection of circulating haematopoietic stem cells for use in bone marrow reconstitution in man.
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PMID:Steroid modulation of naturally occurring diurnal variation in circulating pluripotential haematopoietic cells (CFU-GEMM). 668 46

Although it has been proposed that the circulating granulocyte (PMN) is an effector cell that causes pulmonary vascular injury in the adult respiratory distress syndrome (ARDS), the functional status of PMNs from patients with this disorder has not been previously defined. In the present study we found that PMNs in samples of pulmonary artery blood from patients with ARDS are in a functionally and metabolically activated state. The mean chemotactic index of PMNs from ARDS patients was 172 +/- 22 SEM compared with a mean chemotactic index of 79 +/- 8 of PMNs from normal subjects (p = 0.0001), a 227 +/- 24% increase over the control value. Respiratory burst activity of PMNs, as assessed by the chemiluminescence response (CL), was 151 +/- 12% of control (mean peak CL of PMNs from patients with ARDS, 166 +/- 31 cpm X 10(3); mean peak CL of normal PMNs, 105 +/- 16 cpm X 10(3); p = 0.04), suggesting that granulocytes from patients with ARDS are likely to generate increased quantities of active oxygen metabolites when stimulated. The chemotactic and chemiluminescence responses of PMNs from patients with ARDS were much greater than those of critically ill patients without ARDS, were enhanced in the absence of concurrent bacterial infection, and did not appear to be blunted by recent administration of glucocorticoids. The PMNs from patients with ARDS had increased ratios of intracellular cyclic GMP to cyclic AMP (165 +/- 5% of control, p = 0.0002), which may be related to the enhanced metabolic activity. Release of superoxide anion, a potential mediator of endothelial injury, was increased over that of control by PMNs from 4 of 8 patients with ARDS (mean, 205 +/- 71% of normal). The results suggest that the circulating PMN is in an activated state in patients with ARDS and may be more likely to release active oxygen species and other inflammatory mediators when perturbed, potentially contributing to pulmonary vascular injury and alveolitis.
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PMID:Functional and metabolic activity of granulocytes from patients with adult respiratory distress syndrome. Evidence for activated neutrophils in the pulmonary circulation. 683 52

Since peritonitis remains a serious clinical problem, we have evaluated the prophylactic efficacy of intraperitoneally administered chemotactic substances in murine intraperitoneal infections. The injection of 10 ml of 3% thioglycollate increased the peritoneal white blood cell count of rats from 1.3 +/- 0.1 X 10(6) (mean +/- SEM) to 1.1 +/- 0.1 X 10(7) (mean +/- SEM) cells/ml. This increase in the number of intraperitoneal phagocytes resulted in reduction in mortality caused by an inoculum consisting of E. coli and hemoglobin from 68% in the control group to 29% in the thioglycollate pretreated group (p less than or equal to 0.02). Intraperitoneal injection of N-formyl-methionyl-phenylalanine (FMP), a chemotactically active oligopeptide, increased the intraperitoneal granulocyte count from virtually 0 to 1 X 1.9 +/- 0.53 X 10(4) (mean +/- SEM) cells/ml after 90 minutes. The rats pretreated in such a manner showed a mortality of 51% after an intraperitoneal challenge with an E. coli/hemoglobin inoculum as compared to a mortality of 72% in control animals (p less than or equal to 0.025). Thus, chemotactic substances can effectively increase the number of phagocytes and concurrently induce resistance to an intraperitoneal bacterial challenge.
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PMID:Chemotactic substances in the treatment of experimental intraperitoneal infections. 700 69

Zymosan particles require opsonization for optimal interaction with granulocytes and activation of their respiratory burst. In the present study we evaluated the serum factors necessary for zymosan opsonization. First, zymosan was treated with either normal serum or hypogammaglobulinemic serum (HGS), which is deficient in immunoglobulins (Ig) but has a normal concentration of complement components. Using granulocyte chemiluminescence to assay opsonization, the activity of particles treated with HGS was 66 +/- 1.9% (mean +/- SEM) of that with normal serum (p less than 0.001), suggesting a role of Ig. HGS opsonic activity was restored to normal when the particles were also treated with IgG; however, neither heat-inactivated normal serum (56 degrees C, 30 min) nor pure human IgG alone had opsonic activity. The roles of the classical (CCP) and alternative (ACP) pathways of the complement system were also investigated. ACP activity seemed essential, since inactivation of the ACP (50 degrees C, 30 min) eliminated the activity of normal serum. However, when the ACP was intact, CCP action appeared to participate in opsonization, since selective CCP inactivation with EGTA and MgCl2 reduced the opsonic activity of normal serum by 26 +/- 3.3% (p less than 0.005). Thus, it is concluded that the ACP, CCP, and IgG all participate in zymosan opsonization.
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PMID:The role of complement and IgG on zymosan opsonization. 726 86

Granulocyte adherence in 10 of 15 untreated asymptomatic hyperglycemic diabetic outpatients (mean fasting glucose +/- SEM, 289 +/- 16 mg/100 ml) was 62 +/- 7% of control values. After treatment (2--4 wk) with tolazamide (500 mg daily), adherence to the nylon fiber columns employed in this study returned to control levels in the seven patients whose fasting glucose levels fell, (mean, 192 +/- 16 mg/100 ml) and deteriorated in the three in whom fasting hyperglycemia worsened. Results of this study indicate that, even in some mildly diabetic patients, a reduction in granulocyte adherence similar to that found in insulin-dependent diabetics may impair the inflammatory response.
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PMID:Impaired granulocyte adherence in mildly diabetic patients: effects of tolazamide treatment. 735 29

Although there is a growing body of information available regarding restoration of hematopoiesis with peripheral blood stem cell (PBSC) autografts, few studies have explored this procedure using allografts. In this study with healthy donors, we investigated the feasibility of a protocol for mobilizing PBSC using recombinant human granulocyte colony-stimulating factor (G-CSF) and subsequent bulk depletion of T cells from apheresis-harvested cells. Nine informed healthy donors were given G-CSF subcutaneously at two different dosing schedules (5 micrograms/kg/d in five donors and 2 micrograms/kg/d in four) for 5 consecutive days, and serial changes in blood components, including hematopoietic progenitor cells, were monitored. After 5 days of stimulation with G-CSF, PBSCs were collected by apheresis, and yields were compared. The number of white blood cells (WBC) reached a plateau level on either day 2 (5 micrograms) or 3 (2 micrograms), but the numbers of red blood cells and platelets were not affected. Circulating colony-forming unit-granulocyte/macrophage (CFU-GM) levels started to increase 1 or 2 days after the increase in the WBC count. By performing a 3L apheresis, the number of CFU-GM harvested was 4.6 +/- 3.3 x 10(6) (mean +/- standard error of the mean [SEM]) in the 5-micrograms group and 1.8 +/- 0.7 x 10(6) in the 2-micrograms group. Different procedures for depleting T cells, including the use of L-phenylalanine methyl ester (PME) and flasks coated with anti-CD5/CD8 monoclonal antibodies or neuraminidase-treated sheep red blood cells (SRBC), were also tested on the harvested cells. We found that cell lysis with PME before selective removal of T cells was very effective in reducing the number of cells that required further processing and was suitable for routine use. However, our current procedure resulted in unsatisfactory depletion of T cells (99.5% removal) while retaining hematopoietic progenitor cells (7.5% recovery). Further research is required in this area.
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PMID:Cell processing protocol for allogeneic peripheral blood stem cells mobilized by granulocyte colony-stimulating factor. 752 Mar 92

We describe the development of a new ELISA for the detection of neural endopeptidase 3.4.24.11 (NEP). Neutral endopeptidase 3.4.24.11 was determined in preparations of human granulocytes, mononuclear cells (MNC), and in serum. Human recombinant NEP was used as reference. Specificity of the mAbs was tested using APAAP, FACS analysis, and Western blot analysis. Lysis of the blood cells was performed by incubating the cells with 0.4% Tween-20 and repeated freezing cycles. The minimal detectable dose for recombinant NEP was 15 pg/ml. The recovery was 94 +/- 9%. The NEP was detectable in 15 out of 20 serum samples of 20 volunteers (mean +/- SEM, 245 +/- 88 pg/ml, n = 20)) and in all granulocyte preparations (1176 +/- 138 pg/10(7) cells, n = 20)). The results were reproducible among replicates (CV = 3 +/- 1%, n = 40), dilutions (CV = 8 +/- 2%, n = 5), and assays (CV = 12 +/- 4%, n = 5). With this new ELISA, a simple and reproducible method for the measurement of NEP 3.4.24.11 is described.
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PMID:ELISA for the neuropeptide degrading endopeptidase 3.4.24.11 in human serum and leukocytes. 752 44

Bryostatins, macrocyclic lactones from the marine bryozoan Bugula neritina, are potent antineoplastic agents and multi-potential stimulators of immune cells. We have examined the effects of bryostatins on mediator release from human basophilic leukocytes and human tissue mast cells. Bryostatins 1, 2, and 5 (10 to 3,000 nmol/L) induced histamine secretion from purified and unpurified peripheral blood basophils, whereas they caused no release of peptide-leukotriene C4 from these cells. The rate of histamine release caused by bryostatin 1 was slower than that caused by anti-IgE (t1/2 +/- SEM = 38.2 +/- 4.7 minutes v 8.9 +/- 0.2 minutes; P < .01), whereas the temperature dependence was similar (optimum release at 37 degrees C, approximately 30% less at 30 degrees C, and no release at 22 degrees C or 4 degrees C). The addition of increasing concentrations of extracellular Ca2+ to the medium caused histamine release in the presence of bryostatins. Subeffective concentrations of bryostatins and anti-IgE produced a synergistic effect on histamine release from basophils. Staurosporine, chelerythrine, and calphostin C (0.1 to 10 nmol/L), which are protein kinase C inhibitors, inhibited the histamine secretion activated by bryostatin 1 and tetradecanoylphorbol-acetate (TPA). Preincubation with granulocyte-monocyte colony-stimulating factor (GM-CSF; 1 and 5 nmol/L) and interleukin-3 (IL-3; 10 ng/mL) potentiated the activation of human basophils induced by bryostatin 1. Neither bryostatin 1 nor bryostatin 2 induced the release of histamine from mast cells isolated from human lung or skin tissues. However, brief (10 minutes) preincubation with bryostatin 1 (3 to 300 nmol/L) potently inhibited the histamine secretion induced by anti-IgE from skin or lung mast cells. Bryostatin 1 was a more potent (by approximately 30 times) inhibitor of IgE-mediated histamine release than was TPA. The heterogeneous effects exerted by bryostatins on human basophils and mast cells can be of interest for those designing therapeutic trials using these agents.
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PMID:The antineoplastic bryostatins affect human basophils and mast cells differently. 753 37


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