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)

Polymorphonuclear leukocytes isolated from endotoxin pretreated (0.1 mg/kg 24 hours before) guinea pigs are shown to be hypersensitive and hyperresponsive to the formylated bacterial chemoattractant FMLP in vitro. Dose-response curves for chemiluminescence and beta-glucuronidase release are shifted to the left and maxima are increased. In receptor binding studies the FMLP binding capacity is shown to be enhanced in cells from endotoxin pretreated animals. FMLP (0.3 mg/kg) administered intravenously into anaesthetized and artificially ventilated guinea pigs is shown to induce neutropenia and a biphasic rise of the insufflation pressure. This response is exaggerated in endotoxin pretreated animals. The initial elevation of the airway resistance is cyclooxygenase dependent, whereas the following rise is cyclooxygenase independent and parallels the neutropenia. Histologically PMN's are shown to be trapped in the pulmonary capillaries. This is associated with an intraseptal/interstitial edema. The results illustrate a functional synergism between two important bacterial products, endotoxin and FMLP.
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PMID:Endotoxin pretreatment enhances neutrophil FMLP-receptor binding and activity in guinea pigs. 311 69

Childhood chronic neutropenia with decreased numbers of chemotactic factor receptors as well as defective chemotaxis was first demonstrated in an 8-month-old girl. Chemotactic factor receptors on neutrophils were assayed using tritiated N-formyl-methionyl-leucyl-phenylalanine (3H-FMLP). The patient's neutrophils had decreased numbers of the receptors: numbers of the receptors were 20,000 (less than 3 SD) as compared with those of control cells of 52,000 +/- 6,000 (mean +/- SD) (n = 10). The neutropenia disappeared spontaneously by 28 months of age parallel with the improvement of chemotaxis and increase in numbers of chemotactic factor receptors. These results demonstrate a transient decrease of neutrophil chemotactic factor receptors as one of the pathophysiological bases of a transient defect of neutrophil chemotaxis in this disorder.
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PMID:Decreased numbers of chemotactic factor receptors in chronic neutropenia with defective chemotaxis: spontaneous recovery from the neutrophil abnormalities during early childhood. 357 64

The anti-inflammatory effects of gold compounds include suppression of PMN lysosomal enzyme release. Since lysosomal products can provoke PMN aggregation, we assessed the effect of two gold compounds, auranofin and GST, on suppressing aggregation, degranulation, and metabolic functions of the cells. Aggregation of 1 x 10(7) cytochalasin B-treated PMNs in response to 2 x 10(-7)M FMLP, as assessed by light scattering, was inhibited in a dose-dependent fashion by both drugs. Concentrations of auranofin ranging from 5 to 20 microM caused 30.8% to 89% inhibition, whereas 200 microM GST reduced aggregation by only 32%. FCS or BSA added to suspensions of normal PMNs considerably reduced the gold compound inhibitory effect on PMN aggregation. Cell viability assessed by dye exclusion and lactate dehydrogenase release was unaffected by the drugs. The suppressive activities of the drugs could not be removed by washing the PMNs. Correspondingly, the drugs suppressed lysosomal enzyme release induced by FMLP of PMNs rendered secretory with cytochalasin B. Concentrations of 20 microM auranofin and 200 microM GST resulted, respectively, in a 61.5% and 19.3% reduction of release of lysozyme, 61.7% and 27.1% reduction of beta-glucuronidase, 84.8% and 33.7%s reduction of myeloperoxidase, and 50.0% and 25.0% reduction of lactoferrin. Furthermore, auranofin inhibited 14C-1-glucose oxidation through the hexose monophosphate shunt in response to stimulation by either PMA or methylene blue. The in vivo studies suggested that auranofin could prevent neither neutropenia induced by zymosan-activated serum nor a corresponding rise in plasma lactoferrin levels. These findings suggest that the beneficial effect of gold compounds in rheumatoid arthritis are unlikely to be related to their ability to dampen PMN activation in vivo.
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PMID:Correlation of in vitro and in vivo effects of gold compounds on leukocyte function: possible mechanisms of action. 628 1

Bolus injections of leukotriene B4 (LTB4) at 30-min intervals repeatedly induced similar profound and reversible neutropenias. In contrast, after a 30-min infusion of LTB4, the neutropenia induced by bolus injections of LTB4 was inhibited in a dose-dependent manner; a threshold inhibition was seen at the infusion rate of 10 ng LTB4/min/kg, whereas almost complete inhibition was observed at 50 ng LTB4/min/kg. Steady state arterial plasma concentrations of LTB4 increased proportionally to LTB4 infusion rate, ranging from 0.15 +/- 0.01 nM (control) to 2.80 +/- 0.16 nM (100 ng/min/kg). Extending the infusion period of LTB4 up to 330 min did not result in an enhanced inhibition of the neutropenia in response to bolus injections of LTB4. Reversibility of the desensitization was shown by an almost complete recovery of the neutropenic response within 30 min after cessation of the infusion. The desensitization achieved towards LTB4 showed some specificity, inasmuch as a profound and reversible neutropenia was observed in response to a bolus of either FMLP or C5a under conditions in which sensitivity to LTB4 was lost. These findings suggest that a specific desensitization to LTB4 is feasible in vivo and may constitute a useful approach, in addition to the use of 5-lipoxygenase inhibitors and LTB4 antagonists, to delineate the significance of LTB4 as a mediator of inflammation.
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PMID:In vivo desensitization to leukotriene B4 (LTB4) in the rabbit. Inhibition of LTB4-induced neutropenia during intravenous infusion of LTB4. 838 Jan 89

The activity of the steroid-inducible protein lipocortin-1 (LC1; with a primary sequence of 346 amino acids; also called annexin 1), a fragment corresponding to amino acids 1-188 and a short peptide from the N-terminus (amino acid 2-26) were tested for anti-inflammatory actions in three models of acute inflammation in the mouse in comparison with a mAb anti-CD11b (alpha CD11b). In the mouse air-pouch model LC1, fragment 1-188 and peptide Ac2-26 exhibited powerful inhibitory effects (ED50 approximately 5.2, 38 and 88 micrograms/mouse, respectively) on leukocyte migration elicited by IL-1. LC1 was approximately 200 times more potent than Ac2-26 on a molar basis although both gave maximal inhibitions, in contrast fragment 1-188 only produced a partial dose-response curve. LC1 was approximately 20 times more potent on a molar basis in this assay than the alpha CD11b mAb. Peptide Ac2-26 and the mAb alpha CD11b also blocked cell migration into the air-pouch induced by IL-8 with approximately the same potency. In the mouse skin edema and zymosan peritonitis assays Ac2-26 was inhibitory (ED50 of 200 micrograms/mouse) but less so than the alpha CD11b antibody (ED50 approximately 0.5 mg/mouse). Both LC1 (10 micrograms) and Ac2-26 (200 micrograms) completely blocked FMLP-induced neutropenia in the mouse. Studies using an inactivated LC1 preparation, which binds to the same high affinity binding sites as the biologically active material, indicated that the short peptide acts on the same sites as the native LC1. This study confirms the activity of LC1 in another model of experimental inflammation and suggests that it acts partly through inhibition of leukocyte activation with an overall effect qualitatively comparable to the blocking of CD11b portion of a beta 2-integrin complex. It also shows that peptides derived from the N-terminal domain of LC1 may mimic the activity of the full length molecule and points the way for a new family of anti-inflammatory substances that inhibit leukocyte trafficking.
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PMID:Lipocortin-1 fragments inhibit neutrophil accumulation and neutrophil-dependent edema in the mouse. A qualitative comparison with an anti-CD11b monoclonal antibody. 840 3

We have studied the role of neutrophils and the effects of the chemotactic factor FMLP, using normal, neutropenic (after cyclophosphamide treatment) and C5a desArg-treated unanesthetized rabbits. The intravenous administration of FMLP in normal animals induces transient and dose-dependent hypotension, neutropenia and thrombocytopenia, with a maximal response in 3 minutes. When a bolus of 5 x 10(-9) moles FMLP was administered, maximal arterial hypotension (40 +/- 1.1 v.s. 90 +/- 1.1 mmHg in the controls, P < 0.001) accompanied by a significant increase in central venous pressure (0.89 +/- 0.9 v.s. -2.2 +/- 0.7 mmHg in the controls, P < 0.01) and a decrease in systemic vascular resistance (90 +/- 15.6 v.s 187 +/- 16.4 mmHg/L/min, P < 0.005). Plasma pH and bicarbonate were significantly reduced, with a parallel increase in plasma lactate levels. A similar reduction of arterial blood pressure was also noted in neutropenic animals (31 +/- 3% of pretreatment levels respectively). C5a des Arg caused neutropenia similar to that seen after 5 x 10(-9) moles FMLP (120 +/- 60/mm3 and 170 +/- 25/mm3 respectively), but it did not induce hypotension. These data suggest that simple neutrophil activation is not the mechanism of the FMLP-induced hypotension and that this chemotactic factor may interact with other cell types to produce its effects.
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PMID:Hemodynamic and metabolic effects of intravenous formyl-methionyl-leucyl-phenylalanine (FMLP) in rabbits. 917 5

The disturbances of polymorphonuclear neutrophil leucocytes (PMNLs) may be considered as a one of the causes of chronic or recurrent respiratory tract infections (RTI). The study carried out on patients with chronic or recurrent RTI was aimed at attempting to assess the dependence of clinical manifestations of RTI on nonspecific PMNLs dependent cellular response status. We used the chemiluminescence (CL) assay to study the ability of PMNLs to generate free oxygen forms during phagocytosis process. CL response of PMNLs to chemotactic peptide FMLP in 48 chronic and/or recurrent RTI patients and in 50 healthy blood donors of similar age (control group) was evaluated. RTI do not seem to be dependent on decreased PMNLs count (mild neutropenia was found in 35% of patients), but they may result from impaired function of PMNLs. All the values of CL response in RTI patients were lower than the lowest value observed in control group and ranged from 2.9 to 27.6 x 10(3) cpm/10(3) PMNLs. The lowest of PMNLs CL test value were found in patients with infections of pulmonary tissue (recurrent pneumoniae). The patients with infections of higher parts of respiratory tract (nasal cavity, sinuses, pharynx, trachea and bronchi) did not present such levels of PMNLs function impairment.
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PMID:[Disturbances of polymorphonuclear neutrophil leukocyte chemiluminescence in patients with chronic or recurrent respiratory tract infections]. 948 39