Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Neutrophil”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1978

Mechanisms of attachment of neutrophils to Candida albicans pseudohyphae in the absence of serum, and of subsequent damage to pseudohyphae by microbicidal processes of neutrophils in vitro.

Mechanisms were studied that might explain the attachment and damage to Candida albicans pseudohyphae by neutrophils in the absence of serum. Attachment of neutrophils to pseudo hyphae was inhibited by Candida mannans (1-10 mg/ml), but not by mannose, dextran, chitin, conconavalin A, or highly charged polyamino acids. Contact was also inhibited by pretreatment of Candida before incubation with neutrophils with chymotrypsin, but not trypsin or several inhibitors of proteases. Similar results were obtained with pretreatment of neutrophils, except that trypsin was inhibitory. When pseudohyphae were killed with ultraviolet light, proteinpolysaccharide complexes of mol wt <10,000 were released which appeared to bind to the surfaces of neutrophils and inhibit contact between neutrophils and Candida, as well as other fungi. Damage to Candida by neutrophils was inhibited by agents known to act on neutrophil oxidative microbicidal mechanisms, including sodium cyanide, sodium azide, catalase, superoxide dismutase, and 1, 4 diazobicyclo (2, 2, 2) octane, a singlet oxygen quencher. Neutrophils from a patient with chronic granulomatous disease did not damage Candida at all. However, the hydroxyl radical scavengers mannitol and benzoate were not inhibitory. Cationic proteins and lactoferrin also did not appear to play a major role in this system. Low concentrations of lysozyme which did not damage Candida in isotonic buffer solutions damaged pseudohyphae in distilled water. Isolated neutrophil granules damaged pseudohyphae only with added hydrogen peroxide and halide, and damage occurred only with granule fractions known to contain myeloperoxidase. These findings suggest that neutrophils recognized a molecule on the Candida surface which has a chymotrypsin sensitive protein component, and which may be liberated from the cell surface upon death of organism. The neutrophil receptors for Candida appear to be sensitive to trypsin and chymotrypsin. Damage to Candida by neutrophils occurred primarily by oxidative mechanisms, including the production of superoxide and hydrogen peroxide interacting with myeloperoxidase and halide, as well as singlet oxygen, but did not appear to involve hydroxyl radical. Lysozyme might have an accessory role, under some conditions.

Candida albicans↗
PubMed1979

Neutrophil function in anergic surgical patients: neutrophil adherence and chemotaxis.

Skin test anergy (A) to recall antigens identifies surgical patients at high risk for sepsis. We studied neutrophil function in such patients to assess any alteration in their host defense mechanisms. Neutrophil adherence was measured with a modified adherence assay capable of measuring the adherence of neutrophils in whole blood or purified neutrophil suspensions, and neutrophil chemotaxis was assessed by the Boyeden technique. Twenty-one laboratory controls had a neutrophil adherence of 71.5 +/- 3.8% (mean +/-SD) and chemotaxis of 128.1 +/- 2.4,micro (mean +/-SD). Fifty-four hospitalized patients with normal skin tests had neutrophil adherence of 72.5 +/- 13.1% (p ~ 0.5 relative to control) and chemotaxis of 123.3 +/- 3.1 micro (p ~ 0.5). Twenty three relatively anergic patients had values of 84.3 +/- 7.9% (p < 0.001) and 103.7 +/- 2.0 micro (p < 0.001). Forty five A patients had adherence of 85.0 +/- 7.0% (p < 0.001) and chemotaxis of 90.4 +/- 2.9 micro (p < 0.001). The correlation coefficient between increased neutrophil adherence and decreased chemotaxis r = 0.81 has p < 0.0005. A factor which increased the adherence of normal control neutrophils was found in the plasma but not the serum of anergic patients. Inhibitors of control neutrophil chemotaxis have been shown in both serum and plasma of patients with decreased autologous neutrophil chemotaxis. We propose that this altered neutrophil function (possibly with other defects) in anergic patients may compromise their host defenses and render them susceptible to infection.

Adolescent↗
PubMed1976

Studies on the regulation of the neutrophil chemotactic response using a rapid and reliable method for measuring random migration and chemotaxis of neutrophil granulocytes.

An economic and sensitive test system for measuring random and directional migration of human neutrophils is described. The technique, based on a modified Boyden chamber equipped with a two-filter system, permits a substantial reduction of both incubation time and sample volume. The influence of various technical factors such as the neutrophil concentration in the cell suspension, the incubation time of the chambers, the test concentration of activated plasma or serum, the presence of heparin, and the procedure for separating neutrophils from human peripheral blood, was investigated. Standardized procedures for measuring and reporting neutrophil chemotaxis are proposed. The method has been used to study the significance of factors regulating neutrophil migration such as cytotaxin inactivators and neutrophil immobilizing factors (NIF). Activity of cytotaxin inactivators as assessed in undiluted serum or plasma at pH 7.4, 6.0 or 4.0 was very low. In contrast, potent neutrophil immobilizing activity was found in human serum or diluted plasma. These factors which inhibit migration were accordingly termed neutrophil immobilizing factors of plasma (NIF-P) and neutrophil immobilizing factor of serum (NIF-S). These factors are heat-stable, non-dialysable and of high molecular weight.

Antigen-Antibody Complex↗
PubMed1975

The role of cyclic AMP in the chemotactic responsiveness and spontaneous motility of rabbit peritoneal neutrophils. The inhibition of neutrophil movement and the elevation of cyclic AMP levels by catecholamines, prostaglandins, theophylline and cholera toxin.

Agents known to affect intracellular levels of cyclic AMP in many diverse systems have been tested for their effect on the chemotaxis induced by Escherichia coli culture filtrates, spontaneous motility and cyclic AMP levels of rabbit peritoneal neutrophils. Prostaglandin E1 and A1 but not prostaglandin F2alpha increased neutrophil cyclic AMP levels and, correspondingly, only the former two prostaglandins inhibited chemotaxis. Nevertheless, a quantitative relationship between prostaglandin stimulation of cyclic AMP and inhibition of chemotaxis could not be found. Epinephrine, isoproterenol, and, to a much lesser extent, norepinephrine increased neutrophil cyclic AMP through beta adrenergic stimulation. Only epinephrine and isoproterenol inhibited chemotaxis, but the inhibition was variable and not related to the ability of these catecholamines to increase intracellular cyclic AMP. Cholera toxin increased neutrophil cyclic AMP after a 30-min lag period which paralled its inhibitory effect on chemotaxis and spontaneous motility. However, the effect on chemotaxis require 50 ng/ml of toxin whereas the effect on cyclic AMP was manifested at 2 ng/ml of toxin. Prior to 30-min preincubation there was no effect of even 1250 ng/ml of toxin on either cyclic AMP or chemotaxis. Choleragenoid prevented the effects of toxin on both cyclic AMP and chemotaxis. The bacterial chemotactic factor obtained from E. coli culture filtrates did not effect a measurable change in levels of neutrophil cyclic AMP. The data indicate that even though cyclic AMP is not, in the main sequence of events, triggering the chemotactic response, increases in neutrophil cyclic AMP may modulate the movement and thus the chemotactic responsiveness of the neutrophil.

Animals↗
PubMed1977

Leukocyte migration agarose test for the assessment of human neutrophil chemotaxis. I. Effects of environmental factors on neutrophil migration under agarose.

To apply the leukocyte migration agarose test (LMAT) to the in vitro assessment of human neutrophil chemotaxis, effects of different culture conditions on neutrophil migration under agarose were studied. Presence of either serum or human serum albumin (HSA) in the culture medium was necessary for detectable neutrophil migration. HSA was preferred since heat-stabile chemotactic agents were found to be generated from fresh serum in the presence of agarose. Additional CO2 in the assay milieu could be replaced by decreasing the NaHCO3 concentration of the culture medium. Both the directed and the spontaneous migration rates of neutrophil leukocytes increased when the concentration of agarose was decreased. Area and distance of migration and cumulative cell count of migrated neutrophil leukocytes were suitable for quantitating the neutrophil migration rate.

Adult↗
PubMed1975

Lysosomal enzyme secretion from human neutrophils mediated by cyclic CMP: inhibition of cyclic GMP accumulation and neutrophil function by glucocorticosteroids.

The effects of several glucocorticosteroids on cyclic GMP accumulation, guanylate cyclase activity, calcium influx, lysosomal enzyme secretion, and phagocytosis were studied in human neutrophils. Contact between neutrophils and serum-treated zymosan particles, in the presence of calcium at pH 7.4, triggered these cellular events within five minutes. Each of these neutrophil functions was markedly inhibited by methylprednisolone sodium succinate, triamcinolone acetonide hemisuccinate and paramethasone acetate but was unaffected by two mineralo-corticosteroids. Human neutrophil soluble guanylate cyclase activity was not changed by the glucocorticoids. Inhibition of phagocytosis by, and lysosomal enzyme secretion from, neutrophils by glucocorticosteroids may be the result of a reduction in cyclic GMP accumulation within these cells. The data suggest that glucocorticosteroids inhibit cyclic GMP accumulation in neutrophils by reducing the influx of extracellular calcium into the cells, thereby limiting the availability of intracellular calcium for metabolic processes associated with the accumulation of cyclic GMP.

Aldosterone↗
PubMed1979

Abnormal neutrophil maturation in a neutrophil defect with morphologic abnormality and impaired function.

Neutrophils from a patient with recurrent pyogenic infections since infancy were found to have morphologic abnormalities and impaired functions. The neutrophils had an abnormal nuclear shape, no or few secondary granules, and no alkaline phosphatase activity. Primary granules were normal in number and structure, and were positive for peroxidase. Immature granulocytes were structurally normal. The neutrophils were impaired in chemotaxis and bactericidal capacity. The patient's marrow cells formed increased numbers of granulocytic colonies of small size in culture. Her peripheral leukocytes produced elevated levels of CSA and adherent marrow cells did not inhibit colony formation. These data indicate an intrinsic neutrophil defect which allows normal proliferation of precursor cells, but results in abnormal morphogenesis and impaired function as the cells mature.

Bone Marrow↗
PubMed1979

The in vitro evaluation of certain neutrophil and lymphocyte functions following the ingestion of 150 mg oral dose of levamisole: assessment of the extent and duration of stimulation of neutrophil chemotaxis, protein iodination and lymphocyte transformation.

Certain functions of human blood neutrophils and lymphocytes were investigated at varying time intervals after the ingestion of a single 150 mg dose of levamisole. The functions tested were neutrophil chemotaxis and post-phagocytic metabolic activity and mitogen-induced DNA and protein synthesis of lymphocytes. It was found that levamisole causes a stimulation of neutrophils motility (cell- and serum-associated) and post-phagocytic hexose monophosphate shunt activity and protein iodination. Increased lymphocyte DNA synthesis, but not protein synthesis, to the mitogen phytohaemagglutinin was observed. The stimulation which was detected almost immediately of these neutrophil and lymphocyte functions was still evident 24 hr later but not at 48 hr, indicating that a single oral dose of levamisole can cause the alteration (stimulation) of leucocyte functions which persists until 24--48 hr after intake of the drug.

Chemotaxis, Leukocyte↗
PubMed1978

Postmitotic marrow neutrophils and neutrophil mobilization in man: role of the spleen.

The relationship between postmitotic marrow neutrophils (PMMN) and neutrophil increment in blood after an intravenous dose of 3 mg hydrocortisone/kg was studied in patients with normal-sized spleens and compared with splenectomized and splenomegalic patients. PMMN were quantified from the ferrokinetic measurement of the normoblast number and the PMMN/normoblast ratio in bone marrow biopsy sections. In 12 control patients with normal PMMN the increment was 3.50 +/- 1.13 X 10(9) neutrophils/liter. An excellent correlation was found between the number of PMMN and the maximal neutrophil increment (y = 826x - 1021, r = 0.93, p less than 0.001) among 24 patients with normal spleen size and a wide range of marrow cellularity. Significantly higher responses were observed in 10 splenectomized patients (y = 872x + 1429, r = 0.92, p less than 0.001). The two regression lines were shown to be parallel, indicating a diminution of the response by 2.5 X 10(9) neutrophils/liter in the presence of a normal spleen. In 11 hypersplenic patients the responses were further reduced and more variable. Peak neutrophilia occurred after median values of 2, 3, and 4 hr in the hypersplenic, the control, and the splenectomized group, respectively. These studies indicate that allowing for the different response curves neutrophil increments may be used as an index of PMMN in patients with normal spleen size and in splenectomized patients. They further suggest sequestration of the prematurely released cells by the spleen.

Bone Marrow Cells↗
PubMed2026

ER proteostasis failure in HYOU1 deficiency alters B cells, neutrophils, and interferon signalling.

Hypoxia upregulated 1 (HYOU1) is a stress-inducible ER chaperone. We investigated 2 unrelated patients carrying biallelic HYOU1 variants and presenting with primary immunodeficiency. Patient 1, homozygous for p.Pro444His, displayed failure to thrive, hypoglycemia, B cell lymphopenia, and neutropenia. Patient 2, compound heterozygous for p.Arg262Gln and p.Pro757_Glu758insAla, exhibited recurrent infections, enteropathy, and hypogammaglobulinemia. In Patient 1, while HYOU1 transcription was preserved, the protein was severely reduced. Tunicamycin treatment of dermal fibroblasts showed a blunted unfolded protein response and defective induction of ER stress-responsive genes. Immunophenotyping showed near-absence of circulating B cells, and single-cell RNA sequencing of bone marrow identified an arrest at the pro-B cell stage. Neutrophils displayed hypogranulation and dysregulated IFN- and apoptosis-associated transcriptional signatures, unresponsive to G-CSF. HYOU1 deficiency hence results in ER stress-induced proteostasis failure that simultaneously impairs adaptive immunity through B cell developmental arrest and innate immunity through neutrophil dysfunction and IFN pathway imbalance. This work expands the spectrum of HYOU1 deficiency and further identifies ER proteostasis as a central determinant of immune homeostasis.

Journal Article↗
PubMed1976

In vitro stimulation of neutrophil motility by levamisole: maintenance of cgmp levels in chemotactically stimulated levamisole-treated neutrophils.

Levamisole at concentrations of 10(-3) M or 10(-4) M consistently increased neutrophil random motility and chemokinesis (stimulated random migration). Similar concentrations also increased directional movement of polymorphonuclear leukocytes to both endotoxin-activated serum and hydrolyzed casein. This effect on chemotaxis was due to a true stimulation and was not due solely to increased random movement. The effect of levamisole on the neutrophils could be removed by washing, but persisted if the cells were initially treated with levamisole and serum or endotoxin-activated serum. After neutrophil stimulation with chemotactic factor an initial rise in intracellular cyclic AMP levels was detected which was not influenced by prior levamisole treatment. Intracellular cyclic GMP levels after an initial slight depression, returned to resting levels and gradually diminished over a 60-minute period. Levamisole-treated cells consistently showed higher cyclic GMP levels and it is postulated that by maintaining intracellular cyclic GMP levels, microtubular assembly and cell motility might be enhanced.

Caseins↗
PubMed1978

Neutrophil transfusion: effect of storage and of collection method of neutrophil blood kinetics.

The kinetics in blood of autologous neutrophils collected by phlebotomy, filtration leukapheresis (FL), or intermittent-flow centrifugation (IFC), labeled with 32P-diisopropylfluorophosphate, and stored at 4 degrees C for up to 2 days were measured in 41 normal subjects. Mean initial recovery for unstored IFC cells was 34.0%, compared to 7.9% for unstored FL cells. Blood half-lives were 4.1 and 2.7 hr for unstored IFC and FL cells, respectively. With neutrophils collected by phlebotomy and stored in whole blood for 1-2 days, posttransfusion recoveries and blood half-times were significantly decreased. Storage of both IFC and FL preparations resulted in only moderate kinetic abnormalities in comparison to the unstored cells. These studies indicate that the ability of unstored IFC cells to circulate is basically normal, whereas that of unstored FL cells is significantly impaired. The data further suggest that these neutrophil concentrates might be stored for 1-2 days prior to transfusion.

Blood Preservation↗
PubMed1979

Cholesterol, phospholipids, and fatty acids of normal immature neutrophils: comparison with acute myeloblastic leukemia cells and normal neutrophils.

The lipid composition of immature myeloid cells from the bone marrow of normal persons and myeloblasts from patients with acute myeloblastic leukemia was studied and compared with the lipid composition of normal mature human neutrophils. Total cholesterol, phospholipid, and fatty acid composition was determined on each cell type. The leukemic cells showed decreased total cholesterol and cholesterol-to-phospholipid ratio, increase phosphatidylcholine and phosphatidylinositol, decreased phosphatidylethanolamine, and an increased percentage of unsaturated fatty acids when compared to normal mature neutrophils. A nearly identical pattern was seen in the normal immature myeloid precursors from normal bone marrow. We conclude that the altered lipid composition of acute myeloblastic leukemia cells is related to unexplained factors related to cell age and not to malignancy per se.

Bone Marrow↗
PubMed1979

Neutrophil function in surgical patients: in vitro correlation of abnormal neutrophil chemotaxis by Levamisole.

Cutaneous anergy to recall skin test antigens is associated with decreased polymorphonuclear neutrophil (PMN) chemotaxis (CTX). This decreased PMN chemotaxis is mediated by factors circulating in the sera (AS) from patients with anergy. Levamisole hydrochloride will correct the chemotactic defect of neutrophils from anergic patients, in vitro, from 96.2 +/- 1.2 to 125.1 +/- 1.7 microns at concentrations of 10(-3) M to 10(-18) M. Pretreatment of normal PMN with Levamisole at 10(-4) M will protect them from the chemotactic inhibiting effect of AS. Normal PMN migrating in the normal range, 128.1+/- 2.7 microns, can be made to behave like anergic PMN by treatment with AS. These PMN which now migrate in the anergic range 92.1 +/- 1.7 microns can be converted back to normal by Levamisole treatment at 10(-3) M to 10(-18) M. In 35 surgical patients who demonstrated the spectrum of decreased PMN CTX, the majority toward the anergy level, Levamisole improved the PMN CTX toward normal levels in every instance, while not affecting the CTX of the normally migrating PMN.

Chemotaxis, Leukocyte↗
PubMed1978

Evaluation of the function of polymorphonuclear neutrophils in patients with glomerulonephritis. I. Influence of nitrogen metabolites retention, in renal failure on functional activity of polymorphonuclear neutrophils.

The function of polymorphonuclear neutrophils in two groups of patients with glomerulonephritis was investigated. Patients were divided according to renal efficiency. In the group of 37 patients with renal failure a decrease in chemotactic activity, phagocytal index and iodination activity of leukocytes was observed (as compared with the control group). Our data indicate that renal insufficiency has some influence on the activity of polymorphonuclear neutrophils.

Acute Kidney Injury↗
PubMed1977

A neutrophil-dependent pathway for the generation of a neutral peptide mediator. II. Subcellular localization of the neutrophil protease.

The human neutrophil neutral peptide-generating protease was associated with the plasma membrane marker 5'-nucleotidase on sucrose density gradient centrifugation of sonicates of granule-free fractions following homogenization and velocity sedimentation. The two activities were also associated on sucrose density gradient fractionation of plasma membranes obtained by hypotonic lysis in EDTA containing buffers, a technique which minimizes aggregation. Treatment of fractions containing these enzymatic activities with 1-0 M NaCl separated the neutral peptide-generating proteasein to the eluate while leaving the 5'-nucleotidase in the pellet. Gel filtration of the solubilized neutral peptide-generating protease through Sephadex G-100 in 1-0 M NaCl demonstrated that the protease had an approximate mol. wt of 20,000 while filtration in physiological salt concentrations yielded activity only in the excluded volume. In both cases, there was complete recovery of neutral peptide-generating activity suggesting that the filtration characteristics of the protease were determined by the salt concentration. The solubilized purified protease, the whole cell sonicates, and the intact cells interacted with heat-inactivated plasma to yield the same product, a neutral peptide with a 1000 molecular weight and an isoelectric point of 7-2-7-6. The neutral peptide-generating protease in each instance was inhibited in dose-response fashion by alpha-1-antitrypsin, LBTI, and DFP. Only 30-60% of the protease sites were functional on intact cells as revealed by substrate cleavage or were available to inhibitors. The neutrophil protease which generates neutral peptide is an extrinsic plasma membrane protein with an approximate mol. wt of 20,000 which functions as an ectoenzyme.

Cell Fractionation↗