Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “NEUTROPHILS”

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 271 records · Page 15Linked to original sources
PubMedDate not supplied

Tirofiban administration attenuates platelet and platelet-neutrophil conjugation but not neutrophil degranulation during in vitro VAD circulation.

Ventricular Assist Devices (VADs) have been used as bridges to heart transplantation. However, VAD circulation is complicated by the incidence of thromboembolism, prolonged bleeding, and activation of the inflammatory cascade. We hypothesize that platelet and neutrophil activation are interrelated and linked to the activation of the glycoprotein (GP) IIb/IIIa platelet receptor. The purpose of this study is to evaluate the effects of Tirofiban, a platelet GP IIb/IIIa receptor inhibitor, on platelet and neutrophil activation during simulated VAD circulation. Two groups of five in vitro VAD circuits were simulated with and without Tirofiban using 450 cc of human blood. Blood samples were drawn at specific time intervals up to 72 hours, measuring leukotriene C4 (LTC4), platelet factor four (PF4), and neutrophil elastase. Tirofiban decreased serum levels of PF4 and LTC4 during VAD circulation. Neutrophil elastase secretion was not affected by Tirofiban administration. Preconditioning of VAD circulation with Tirofiban attenuated platelet activation as demonstrated by a decrease in serum PF4 levels. Tirofiban administration ameliorates the inflammatory response by altering platelet-neutrophil interaction as demonstrated by a decrease in LTC4 production. Continued elastase secretion indicates that the inflammatory response is not completely inhibited by Tirofiban administration. These results suggest that neutrophils may be activated by alternative mechanisms. Early complement activation has been demonstrated during in vivo and in vitro VAD circulation and may play a role in mediating inflammatory and thromboembolic reactions during VAD use.

Blood Platelets↗
PubMed1990

Neutrophil-potentiating factors released from stimulated lymphocytes; special reference to the increase in neutrophil-potentiating factors from streptococcus-stimulated lymphocytes of patients with Behçet's disease.

The potentiating effect of the soluble factors released from normal or diseased lymphocytes on neutrophil functions were investigated in the presence or absence of mitogens and wall preparations of Streptococcus pyogenes. When normal T lymphocyte populations were stimulated with T cell mitogens or with streptococcal preparations, the supernatants from these cultures potentiated neutrophil chemotaxis, phagocytosis and O2- generation. Upon gel-filtration of these stimulated lymphocyte supernatants, the neutrophil-potentiating activity was inactivated by trypsin or by a 30-min incubation at 130 degrees C, but was not affected by acid treatment at pH 2 or heat treatment at 56 degrees C for 60 min. Its activity was almost not affected by antisera against human interleukin-1, interleukin-2, interferon-gamma or tumour necrosis factor. With the stimulation of T cell mitogens, the supernatants released from the lymphocytes of not only the patients with Behçet's disease but also healthy and diseased controls enhanced neutrophil functions. However, supernatants from streptococcal preparation-stimulated lymphocytes from patients with Behçet's disease had a higher potentiating effect on neutrophil functions. Our study suggests that the enhanced neutrophil functions in patients with Behçet's disease may be related to an abnormally high level of circulating activated T cells in these patients.

Adult↗
PubMed1992

Activation of normal neutrophils by anti-neutrophil cytoplasm antibodies.

Anti-neutrophil cytoplasm antibodies (ANCA) are markers of systemic vasculitis for which a pathogenetic role has been postulated. We have examined the effect of these autoantibodies on the function of normal human neutrophils in vitro. In the presence of ANCA positive sera luminol-amplified chemiluminescence was significantly increased compared to the values seen in the presence of normal or anti-double stranded DNA positive sera (P < 0.01). Five of six ANCA positive F(ab)2 preparations also produced significant neutrophil activation as demonstrated by the chemiluminescence response. This response was totally abrogated by the addition of neutrophil cytoplasm extract, containing the ANCA antigen. Addition of inhibitors to the chemiluminescence system demonstrated that the chemiluminescence response was inhibited by azide and salicylhydroxamic acid and reduced by histidine, suggesting that the chemiluminescence response was due to activation of myeloperoxidase, with generation of singlet oxygen. The chemotactic response to f-Met-Leu-Phe, a bacterial chemotactic peptide, was significantly augmented in the presence of ANCA. Chemotaxis to zymosan-activated serum and chemokinesis was not affected. Phagocytosis was also unaffected. We propose that neutrophil activation and modulation of neutrophil migration by ANCA may be of pathogenetic significance in systemic vasculitis.

Antibodies, Antineutrophil Cytoplasmic↗
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↗
PubMed1987

Fatty-acid-induced activation of NADPH oxidase in plasma membranes of human neutrophils depends on neutrophil cytosol and is potentiated by stable guanine nucleotides.

Both cis and trans unsaturated fatty acids and sodium dodecyl sulfate activated NADPH oxidase in plasma membranes of human neutrophils in the presence of neutrophil cytosol. In contrast, 5,8,11,14-icosatetraynoic acid, saturated fatty acids, esters, peroxides and 4 beta-phorbol 12-myristate 13-acetate, a potent activator of protein kinase C, were inactive. 5,8,11,14-icosatetraynoic acid inhibited superoxide formation elicited by fatty acids. Guanosine 5'[gamma-thio]triphosphate (GTP[gamma S]), a potent activator of guanine-nucleotide-binding proteins (N-proteins) enhanced superoxide formation elicited by fatty acids up to fourfold, supporting our previous suggestion that NADPH oxidase is regulated by an N-protein [Seifert, R. et al. (1986) FEBS Lett. 205, 161-165]. Cytosols from various tissues, soybean lipoxygenase and protein kinase C, purified from chicken stomach, did not substitute neutrophil cytosol. The activity of neutrophil cytosol was destroyed by heating at 95 degrees C. Superoxide formation was not affected by the inhibitor of protein kinase C 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7). Removal of cytosolic ATP by preincubation with hexokinase and glucose, dialysis of neutrophil cytosol or chelation of calcium with EGTA did not abolish the stimulatory effect of arachidonic acid and GTP[gamma S]. Thus, the cytosolic cofactor appears to be a neutrophil-specific and heat-labile protein, which is neither a lipoxygenase nor protein kinase C.

Cell Membrane↗
PubMed2004

Significance of human neutrophil antigen-2a (NB1) expression and neutrophil number in pregnancy.

BACKGROUND: Expression of human neutrophil antigen-2a (HNA-2a) is greater in women than in men. The size of the HNA-2a-positive neutrophil population increases with pregnancy. STUDY DESIGN AND METHODS: T he relationship between HNA-2a expression on neutrophils and monocytes, and their relative numbers, was investigated. HNA-2a expression shown as the size of the HNA-2a-positive cell population and the fluorescence intensity on the cells was analyzed using flow cytometry. This investigation was done among 165 pregnant women during pregnancy and postpartum. RESULTS: In normal pregnancy, numbers of neutrophils and monocytes changed in relation to HNA-2a expression. HNA-2a was also expressed intensively on monocytes from some pregnant women in the first and second trimesters. HNA-2a expression and the number of cells markedly decreased postpartum. In threatened premature labor, the number of neutrophils decreased earlier than in normal pregnancy. CONCLUSION: HNA-2a expression may increase soon after fertilization. In this study, the results indicate that the change in the number of neutrophils and monocytes is related to HNA-2a expression.

Adult↗
PubMedDate not supplied

Incidence of neutrophil antigens on human cord neutrophils.

Neutrophils isolated from cord blood of healthy newborns (33 blacks and 21 whites) were investigated by EDTA-microagglutination for their expression of neutrophil specific antigens that have been associated with isoimmune neonatal or autoimmune neutropenia. Equal volumes of various neutrophil antisera (2 microliter) and cord neutrophils (3-5 X 10(6)/ml) were mixed in tissue typing microplates under oil and were incubated at room temperature for 6-8 hr, following which the degree of agglutination was noted. Our data revealed that all the currently recognized neutrophil antigens are readily demonstrable by antineutrophil antibodies in cord blood, (NA1, 52-54%; NA2, 81-85%; NB1, 95-96%; NC1, 90%; 9A, 29-30%) suggesting that neutrophil antigens are fully expressed at birth.

Antigens, Surface↗
PubMed2006

Granulocyte and monocyte adsorption apheresis (GCAP) for refractory skin diseases caused by activated neutrophils and psoriatic arthritis: evidence that GCAP removes Mac-1-expressing neutrophils.

In the present study, we have shown that granulocyte and monocyte adsorption apheresis (GCAP), an extracorporeal apheresis instrument whose column contains cellulose acetate (CA) beads, is useful for skin diseases attributable to activated granulocytes and psoriatic arthritis (PsA). We assessed the clinical effectiveness of GCAP and investigated the mechanisms underlying the adsorption of pathogenic granulocytes. The effect of GCAP was assessed in 14 patients with neutrophilic dermatoses and 16 with PsA. The mechanisms by which the instrument adsorbs activated granulocytes were investigated using an in vitro mini-column system that mimics the GCAP. Skin lesions and arthropathy improved in 22 of 29 patients (75.9%) and 14 of 18 (77.8%), respectively. Mac-1 (CD11b/CD18) expression on the peripheral neutrophils, increased compared with normal subjects, was reduced by GCAP. In the mini-column system, CA beads adsorbed 50% neutrophils; and adsorption was inhibited significantly by treating plasma with EDTA and blood cells with antihuman CD11b monoclonal antibody. GCAP was useful for treating neutrophilic dermatoses and PsA. GCAP adsorbs Mac-1-expressing neutrophils to the CA beads by the binding of complement component (iC3b) on CA beads and CD11b expressed on activated neutrophils.

Adsorption↗
PubMed2001

Chemokine-dependent neutrophil recruitment in a murine model of Legionella pneumonia: potential role of neutrophils as immunoregulatory cells.

The roles of CXC chemokine-mediated host responses were examined with an A/J mouse model of Legionella pneumophila pneumonia. After intratracheal inoculation of 10(6) CFU of L. pneumophila, the bacterial numbers in the lungs increased 10-fold by day 2; this increase was accompanied by the massive accumulation of neutrophils. Reverse transcription-PCR data demonstrated the up-regulation of CXC chemokines, such as keratinocyte-derived chemokine, macrophage inflammatory protein 2 (MIP-2), and lipopolysaccharide-induced CXC chemokine (LIX). Consistent with these data, increased levels of KC, MIP-2, and LIX proteins were observed in the lungs and peaked at days 1, 2, and 2, respectively. Although the administration of anti-KC or anti-MIP-2 antibody resulted in an approximately 20% decrease in neutrophil recruitment on day 2, no increase in mortality was observed. In contrast, the blockade of CXC chemokine receptor 2 (CXCR2), a receptor for CXC chemokines, including KC and MIP-2, strikingly enhanced mortality; this effect coincided with a 67% decrease in neutrophil recruitment. Interestingly, anti-CXCR2 antibody did not affect bacterial burden by day 2, even in the presence of a lethal challenge of bacteria. Moreover, a significant decrease in interleukin-12 (IL-12) levels, in contrast to the increases in KC, MIP-2, and LIX levels, was demonstrated for CXCR2-blocked mice. These data indicated that CXCR2-mediated neutrophil accumulation may play a crucial role in host defense against L. pneumophila pneumonia in mice. The increase in lethality without a change in early bacterial clearance suggested that neutrophils may exert their protective effect not through direct killing but through more immunomodulatory actions in L. pneumophila pneumonia. We speculate that a decrease in the levels of the protective cytokine IL-12 may explain, at least in part, the high mortality in the setting of reduced neutrophil recruitment.

Animals↗
PubMed2003

Selective transport of cytokine-induced neutrophil chemoattractant from the lung to the blood facilitates pulmonary neutrophil recruitment.

The CXC chemokines cytokine-induced neutrophil chemoattractant (CINC) and macrophage inflammatory protein-2 (MIP-2) are potent neutrophil chemoattractants in rats. We have previously shown that CINC, unlike MIP-2 and most other proinflammatory cytokines, is elevated in the systemic circulation in response to an intratracheal (IT) challenge. Therefore, we hypothesized that CINC generated within the lung selectively enters the vascular compartment to facilitate pulmonary neutrophil recruitment. Rats were administered IT LPS, and plasma CINC and MIP-2 levels were measured 90 min and 4 h after injection, along with mRNA expression in lung, spleen, liver, and kidney. Ninety minutes and 4 h after IT LPS, CINC and MIP-2 mRNA expression were largely confined to lung homogenate, but of the two chemokines, only CINC was present in plasma. In separate experiments, rats received IT injections of recombinant CINC and/or MIP-2. Here, plasma levels of CINC, but not MIP-2, were significantly increased throughout the 4-h observation period. This finding was verified by individually administering (125)I-labeled forms of each chemokine. Instillation of recombinant MIP-2 or CINC into the lung increased the number of neutrophils recovered in bronchoalveolar lavage fluid at 4 h, and this effect was enhanced when both chemokines were administered together. In addition, intravenous (IV) CINC, but not IV MIP-2, increased pulmonary neutrophil recruitment in response to IT MIP-2. Our results show that CINC, in contrast to MIP-2, is selectively transported from the lung to the systemic circulation, where it promotes neutrophil migration into the lung in response to a chemotactic stimulus.

Animals↗
PubMedDate not supplied

Killing of gram-negative bacteria by ciprofloxacin within both healthy human neutrophils and neutrophils with inactivated O2-dependent bactericidal mechanisms.

The intraphagocytic killing of Escherichia coli, Serratia marcescens, Pseudomonas aeruginosa, and Salmonella typhi by ciprofloxacin (0.1, 1 and 5 microg/ml) within human neutrophils with intact and impaired (by phenylbutazone treatment) O2-dependent killing mechanisms was studied and compared with the extracellular killing in the same medium of the intraphagocytic killing, but omitting neutrophils. The MIC/MBC of ciprofloxacin in vitro (assays performed according to NCCLS specifications) were: 0.015/0.06 for E. coli, 0.12/32 for S. marcescens, 1/16 for P. aeruginosa, and 0.007/0.06 for S. typhi. Ciprofloxacin showed bactericidal activity both extracellular and within phenylbutazone-treated and untreated neutrophils. The minimum concentration of ciprofloxacin to kill 90% of phagocytosed bacteria within neutrophils with normal O2-dependent killing power after 30 min was: 0.1 microg/ml for E. coli, and S. typhi, 1 microg/ml for P. aeruginosa, and 5 microg/ml for S. marcescens. In contrast, exposure for 60 min was required to reach this percentage within phenylbutazone treated neutrophils. The minimum concentration to kill 90% of extracellular bacteria after 30 min was: 0.1 microg/ml for E. coli, P. aeruginosa and S. typhi, and 5 microg/ml, for S. marcescens. A positive interaction between ciprofloxacin and the O2-dependent mechanisms of phagocytes was found. The reactive oxygen metabolites produced in the respiratory burst did not affect the intraphagocytic activity of ciprofloxacin. Phenylbutazone treatment of phagocytes would be a good experimental model to study the intraphagocytic killing of drugs in situations such as AIDS and chronic granulomatous disease where inefficient oxidative mechanisms of neutrophils exist.

Anti-Infective Agents↗
PubMed1990

Elevation of neutrophil chemotactic activity in the human serum and the decreased number of neutrophils after platelet-activating factor inhalation.

We previously reported a significant decrease in neutrophils at 5 min and an increased number of neutrophils at 15 min after PAF-acether inhalation. To investigate the mechanism, we measured the neutrophil chemotactic activity of the sera. Neutrophil chemotactic activity (NCA) of the serum at 5 min was greater than at baseline (p less than 0.01) or at 15 min (p less than 0.05). Furthermore, we investigated the correlation between the change in NCA and decreased number of neutrophils. A significant correlation was found between these two at 5 min (r = 0.751, p less than 0.05). These data suggest that an elevation of NCA may play an important role in the decrease of circulating neutrophils after PAF-acether inhalation.

Administration, Inhalation↗
PubMed1995

Characterization of leukocyte-derived neutrophil chemotactic factor-2 and its possible roles in neutrophil infiltration in allergic inflammation in rats.

This study sought to clarify the responsible chemotactic factor for neutrophils in allergic inflammation in rats. When the leukocytes collected from the pouch fluid 4 h after injection of the antigen solution into the air pouch were incubated, the neutrophil chemotactic activity in the conditioned medium increased time-dependently with higher levels for the leukocytes from the immunized rats than the nonimmunized ones. The chemotactic activity did not result from cytokine-induced neutrophil chemoattractant (CINC) because CINC concentrations in the conditioned medium were low. Neutrophil chemotactic factors in the conditioned medium were separated by isoelectric focusing into two factors, leukocyte-derived neutrophil chemotactic factor (LDNCF)-1 and LDNCF-2. The activity of LDNCF-2 was more than 75% of the total chemotactic activity in the conditioned medium. LDNCF-2 was purified by gel chromatography and reverse-phase HPLC. The N-terminal amino acid sequence (1-20) of the purified LDNCF-2 was identical to the 32-51 amino acid sequence of the pro-form of rat macrophage inflammatory protein (MIP)-2. Higher levels of MIP-2 mRNA in the leukocytes from the immunized rats than that from the non-immunized rats were proved by the reverse transcription-polymerase chain reaction. In vivo, concentrations of CINC in the pouch fluid were low, and did not represent the chemotactic activity in the pouch fluid. These results suggest that LDNCF-2 (MIP-2) is an important chemotactic factor for neutrophils in the allergic inflammation in rats.

Amino Acid Sequence↗
PubMed1988

Mepacrine impairs neutrophil response after acute lung injury in rats. Effects on neutrophil migration.

Intraalveolar leukocytosis is integral in initiating and perpetuating airspace inflammatory reactions. We used intratracheal instillation of silica suspensions in adult male rats to cause neutrophil flux (32% increase over saline controls) without creating a protein leak, so simulating an early inflammatory response. We examined the in vivo effects of a known phospholipase A2 inhibitor (mepacrine) and the two mast cell active agents (cyproheptadine and reserpine) on lung lavage fluid chemotactic capability, alveolar macrophage (AM) production of chemotactic factor(s), and neutrophil diapedesis. Only mepacrine significantly depressed the leukocytosis (from 32% to 8% of total cells), with a similar diminution in AM chemotaxin production. Separate in vitro experiments using mepacrine-pretreated neutrophils and macrophages gave evidence that mepacrine: (1) diminishes neutrophil response to chemotaxin(s), (2) inhibits spontaneous, random neutrophil movement, and (3) diminishes macrophage-derived chemotactic factor production. These observations suggest that the earliest events in alveolar inflammatory reactions probably involve local production of chemotactic factors by AM, and that mepacrine's anti-inflammatory action results from inhibitory influences on both macrophage and neutrophil populations.

Acute Disease↗
PubMed1992

Erythromycin reduces neutrophils and neutrophil-derived elastolytic-like activity in the lower respiratory tract of bronchiolitis patients.

Diffuse panbronchiolitis (DPB) is a disease of adults characterized by chronic inflammation of the respiratory bronchioles and the infiltration of chronic inflammatory cells. The clinical efficacy of erythromycin therapy has been demonstrated in DPB patients, but the mechanism of action of this drug is unknown. We investigated the localization of neutrophils in lung biopsy specimens, as well as the cell population and elastolytic-like and chemotactic activity of bronchoalveolar lavage (BAL) fluid, before and after treatment with erythromycin or ampicillin in 11 DPB patients (six biopsy-proven and five clinically diagnosed) and one follicular bronchiolitis patient. These bronchiolitis patients had a high percentage of neutrophil and a high neutrophil-derived elastolytic-like activity in BAL fluid compared with chronic bronchitis patients and normal control subjects. The number of neutrophils and the neutrophil-derived elastolytic-like activity in BAL fluid decreased significantly after treatment with erythromycin along with a significant improvement in pulmonary function studies, although there was no significant change in the chemotactic activity of BAL fluid. No significant reduction in BAL fluid neutrophilia was found in the ampicillin-treated patients. These results suggest an important role for the neutrophil in the pathogenesis or development of bronchiolitis, and also suggest that erythromycin may be useful for the treatment of bronchiolitis through its direct action upon host phagocytic cells.

Adolescent↗
PubMed1983

Human neutrophil elastase does not bind to alpha 1-protease inhibitor that has been exposed to activated human neutrophils.

The effect of leukocyte-derived oxidants on the elastase-inhibitory capacity of alpha 1-protease inhibitor was examined in an in vitro system using cells and purified proteins from human sources. The exposure of alpha 1-protease inhibitor to the myeloperoxidase-hydrogen peroxide-halide system resulted in a nearly complete loss of its ability to bind and inactivate purified human neutrophil elastase. A similar loss of binding to and inactivation of human neutrophil elastase was observed on exposure of alpha 1-protease inhibitor to human neutrophils in the presence of a halide and the neutrophil-activating agent, phorbol myristate acetate. This loss of elastase binding activity was abrogated by the addition of azide or catalase but not superoxide dismutase or heated catalase. The data suggest oxidative inactivation of alpha 1-protease inhibitor by secreted myeloperoxidase and hydrogen peroxide. Thus, the reported effects of leukocyte oxidants, especially the myeloperoxidase system, on alpha 1-protease inhibitor have been confirmed using the most pathophysiologically relevant protease, human neutrophil elastase, as the test enzyme. The role of the neutrophil in the pathogenesis of emphysema may, therefore, include the secretion of both elastase and oxidants that impair antielastase defenses.

Blood Proteins↗
PubMed1984

Neutrophils kill pulmonary endothelial cells by a hydrogen-peroxide-dependent pathway. An in vitro model of neutrophil-mediated lung injury.

Neutrophil-mediated injury to lung parenchymal cells has been proposed as an important step in the pathogenesis of many acute and chronic lung disorders. As an in vitro model of neutrophil-mediated injury, this study used activated human neutrophils as effector cells in an 18-h cytotoxicity assay with 51Cr-labeled bovine pulmonary artery endothelial cells serving as target cells. Neutrophils effectively injured pulmonary endothelial cells, expressed as cytotoxic index (CI), of 63.8 +/- 5.4, and this injury could be significantly reduced by several agents, including 1% dimethyl sulfoxide (CI, 51.3 +/- 3.7), 50 micrograms/ml ascorbic acid (CI, 40.8 +/- 4.7), and especially 1,100 U/ml catalase (CI, 14.3 +/- 4.1). As cell-free models of neutrophil-mediated endothelial cell injury, H2O2 (30 microM), O2- (generated by 0.5 mU xanthine oxidase), and the myeloperoxidase-dependent (0.32 U) hypohalite ion were each capable of injuring the target cells with CI of 6.21 +/- 2.8, 53.6 +/- 5.3, and 21.2 +/- 1.5, respectively. Catalase was effective in reducing the injurious effect of each of these oxidant-generating systems (p less than 0.01, all comparisons), confirming the important role for H2O2 in the mediation of this injury. The data indicate that neutrophils are capable of killing pulmonary endothelial cells by a pathway largely dependent on the generation of H2O2, and suggest the possibility that removal of H2O2 from the alveolar structures in subjects with these disorder might be an effective future therapeutic approach.

Animals↗
PubMed1981

Lactoferrin enhances hydroxyl radical production by human neutrophils, neutrophil particulate fractions, and an enzymatic generating system.

During phagocytosis, neutrophils take oxygen from the surrounding medium and convert it to superoxide anion (O2-) and hydrogen peroxide (H2O2). Hydroxyl radical (.OH), a particularly potent oxidant, is believed to be produced by interaction between O2- and H2O2 in the presence of iron, according to the Haber-Weiss reactions. Production of .OH by whole human neutrophils, by particulate fractions from human neutrophils disrupted after stimulation, and by a xanthine oxidase system was measured by conversion of alpha-keto-gamma-methiol butyric acid to ethylene. FeCl3 or ferric EDTA enhanced ethylene production in all three systems by 155--406% of base line at a concentration of 50--100 microM. Iron-saturated human milk lactoferrin, 100 nM, increased ethylene generation by 127--296%; and purified human neutrophil lactoferrin, 10 nM, enhanced ethylene production by 167--369%. Thus, iron bound to lactoferrin was approximately 5,000 times more effective in producing an enhancement in ethylene generation than iron derived from FeCl3 or ferric EDTA. O2- and H2O2 were required for ethylene production in the presence of lactoferrin, since superoxide dismutase inhibited ethylene formation in the three systems by 76--97% and catalase inhibited by 76--98%. Ethylene production in the presence of lactoferrin was inhibited by the .OH scavengers mannitol, benzoate, and thiourea by 43--85, 45--94, and 76--96%, respectively. Thus, most of the ethylene production could be attributed to oxidation of alpha-keto-gamma-methiol butyric acid by .OH. The ability of neutrophil lactoferrin to provide iron efficiently to the oxygen radical-generating systems is compatible with a role for lactoferrin as regulator of .OH production. As such, lactoferrin may be an important component in the microbicidal activity of neutrophils.

Benzoates↗