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At least 19 recordsLinked to original sources
PubMed2000

The ability of Helicobacter pylori to activate neutrophils is determined by factors other than H. pylori neutrophil-activating protein.

The ability of Helicobacter pylori to activate neutrophils is associated with peptic ulcer disease (PUD). One of the H. pylori factors previously suggested to stimulate neutrophil activation is the H. pylori neutrophil-activating protein (HpNAP). The primary aims of this study were to investigate the relationships between H. pylori neutrophil activation and reported variations in HpNAP expression and the napA gene sequence. The association between neutrophil activation and vacuolating cytotoxin activity was also investigated. The ability to activate neutrophils was found here to be associated with the development of PUD and was a characteristic more frequently identified in H. pylori isolates with vacuolating cytotoxin activity. However, no relationship was found between neutrophil activation and the expression of HpNAP or differences in the napA sequence. In conclusion, the ability to activate neutrophils contributes to the ulcerative potential of individual H. pylori isolates, but this activity is not mediated by differences in HpNAP.

Bacterial Proteins↗
PubMed1993

Activated neutrophils and neutrophil activators in human milk: increased expression of CD11b and decreased expression of L-selectin.

Human milk neutrophils and macrophages were examined by flow cytometry to determine whether they displayed phenotypic markers of activation. The markers were CD11b and L-selectin, which are increased or shed, respectively, from the surface of activated neutrophils. Phenotypic features of milk neutrophils and macrophages were similar to blood neutrophils stimulated with fMLP: plasma membrane expression of CD11b was increased and L-selectin was decreased. After blood neutrophils were incubated in acellular milk, their expression of CD11b increased and L-selectin decreased. The activation was not affected by trypsin but was significantly decreased by treating acellular milk with chloroform or ether. Sedimentation studies suggested that particulate fractions of milk were active. Further, the activation was partly blocked by treating target blood neutrophils with cytochalasin B. Thus, human milk neutrophils are activated, and the activation may be due partly to phagocytosis of membranous structures in milk.

Cell Adhesion Molecules↗
PubMed2002

Adhesion of normal erythrocytes at depressed venous shear rates to activated neutrophils, activated platelets, and fibrin polymerized from plasma.

Deep vein thrombosis (DVT) is a low flow pathology often prevented by vascular compression to increase blood movement. We report new heterotypic adhesive interactions of normal erythrocytes operative at low wall shear rates (gamma(w)) below 100 s(-1). Adhesion at gamma(w) = 50 s(-1) of washed red blood cells (RBCs) to fibrinogen-adherent platelets was 4-fold less (P <.005) than to collagen-adherent platelets (279 +/- 105 RBC/mm(2)). This glycoprotein VI (GPVI)-triggered adhesion was antagonized (> 80% reduction) by soluble fibrinogen (3 mg/mL) and ethylenediaminetetraacetic acid (EDTA). RBC-platelet adhesion was reduced in half by antibodies against CD36 or GPIb, but not by antibodies against GPIIb/IIIa, von Willebrand factor (VWF), thrombospondin (TSP), P-selectin, beta(1), alpha(v), or CD47. Adhesion of washed RBCs to fibrinogen-adherent neutrophils was increased 6-fold in the presence of 20 microM N-formyl-Met-Leu-Phe to a level of 67 RBCs per 100 neutrophils after 5 minutes at 50 s(-1). RBC-neutrophil adhesion was diminished by anti-CD11b (76%), anti-RBC Landsteiner-Wiener (LW) (ICAM4; 40%), or by EDTA (> 80%), but not by soluble fibrinogen or antibodies against CD11a, CD11c, CD36, TSP, beta(1), alpha(v), or CD47. RBC adhesion to activated platelets and activated neutrophils was prevented by wall shear stress above 1 dyne/cm(2) (at 100 s(-1)). Whereas washed RBCs did not adhere to fibrin formed from purified fibrinogen, adhesion was marked when pure fibrin was precoated with TSP or when RBCs were perfused over fibrin formed from recalcified plasma. Endothelial activation and unusually low flow may be a setting prone to receptor-mediated RBC adhesion to adherent neutrophils (or platelets/fibrin), all of which may contribute to DVT.

Blood Platelets↗
PubMed1998

Reduction of acute and reactivated colitis in rats by an inhibitor of neutrophil activation.

Neutrophils have been implicated as major contributors to tissue injury in inflammatory bowel disease. In this study, we have assessed the effects of an inhibitor of neutrophil activation and adherence, NPC-18915 (4-¿2-[2-(2-benzofuranyl)phenyl]-(E)-ethenyl¿benzoic acid sodium salt), in models of both acute and reactivated colitis. Acute colitis was induced by intracolonic administration of a hapten. In other rats, colitis was reactivated 6 wk after a bout of acute colitis by subcutaneous administration of the hapten. NPC-18915 given during the first 4 days after induction of acute colitis significantly reduced tissue injury and the incidence of diarrhea and adhesions. When treatment of NPC-18915 was initiated after colitis was firmly established (48 h posthapten), it did not produce a significant effect. NPC-18915 was effective at significantly reducing colonic injury and granulocyte infiltration in the reactivated colitis model, and a similar effect could be observed in rats treated with antineutrophil serum. These results demonstrate that an inhibitor of neutrophil activation is effective in both acute and reactivated colitis, although in the former case, effectiveness is only seen when the drug is given before full establishment of colitis. These results also suggest that neutrophils, are a critical effector cell of hapten-induced colitis in the rat, particularly in the case of reactivated colitis.

Acute Disease↗
PubMed1989

Limitation of myocardial reperfusion injury by intravenous perfluorochemicals. Role of neutrophil activation.

Neutrophil activation and infiltration into the ischemic myocardium after reperfusion may limit the amount of salvageable myocardium (reperfusion injury). The effects of intravenous perfluorochemicals (Fluosol-DA) on infarct size, ventricular contractility, and neutrophil function were assessed in an occlusion-reperfusion canine model. Closed-chest dogs were subjected to 90 minutes of left anterior descending artery occlusion followed by 24 hours of reperfusion. Animals were randomized to receive either Fluosol-DA (FDA, n = 8) or Ringer's lactate (CONT, n = 10) intravenously over 30 minutes just before left anterior descending artery reperfusion. Neutrophil demargination and infiltration into the myocardium were assessed in vivo with In111. Neutrophil chemotaxis, superoxide radical production, and lysozyme degranulation were evaluated ex vivo at baseline, 1 hour after occlusion, and 1 hour after reperfusion. Perfluorochemicals significantly reduced infarct size expressed as percent of area at risk (FDA, 7 +/- 4%; CONT, 24 +/- 6%; p less than 0.01). This was associated with positive wall motion in the jeopardized zone of Fluosol-DA animals compared with dyskinesis in control animals (FDA, +4.4 +/- 2.1%; CONT, -1.1 +/- 1.5%; p less than 0.05). Electron microscopy showed reduced neutrophil and erythrocyte plugging of capillaries with relative preservation of endothelial cells in the Fluosol-DA animals. Myocardial blood flow was greater in the ischemic endocardium of Fluosol-DA animals 1 hour after reperfusion (FDA, 1.23 +/- 0.21; CONT, 0.62 +/- 0.08 ml/g/min; p less than 0.01). Neutrophil demargination and infiltration into the ischemic myocardium was reduced in the animals treated with Fluosol-DA. (FDA, 2.5 +/- 0.7 x 10(3); CONT, 14.1 +/- 2.7 x 10(3) neutrophils/g; p less than 0.01). Neutrophil chemotaxis and lysozyme release were also markedly suppressed in the Fluosol-DA groups ex vivo. These results show that intravenous Fluosol-DA significantly reduces reperfusion injury with greater salvage of myocardium and improved left ventricular function. The chief mechanism of action of Fluosol-DA appears to be the suppression of neutrophil function.

Animals↗
PubMed1984

Rheumatoid arthritis. The role of neutrophil activation.

Neutrophils constitute over 90% of cells found in the synovial fluid of rheumatoid arthritis (RA) patients. Since such fluids also contain immune complexes (IgG-IgG and IgG-IgM rheumatoid factors) and complement split products (C5, C5A, DES, ARG, C3B, etc.), all of the reactants are present for a local Arthus lesion. Moreover, neutrophils from RA patients endocytose these immune complexes and complement components in vivo and in vitro. In consequence, it has been suggested that lysosomal enzymes and other mediators of inflammation released by neutrophils after uptake of immune complexes (in the bulk phase or on the surface) account, at least in part, for rheumatoid inflammation. Secretion of lysosomal hydrolases, especially neutral proteases, which provoke tissue injury and generation of reactive oxygen species (e.g. O2) is part of a stimulus-secretion response to a variety of secretagogues, including immune complexes and complement components. However, the pathways of secretion and O2 generation are stimulus-specific and can be dissected to establish cause and effect relationships by (a) kinetic analysis, (b) varying the stimulus, (c) use of impermeant reagents to block discrete responses. Neutrophils also generate products of 11-cyclo-oxygenase (e.g., PGE2, TXA2) and of the 5- and 15-lipoxygenase (mono-, di and tri-hetes, LTB4 and their isomers). However, the cyclo-oxygenase products (except TXA2) do not cause inflammation acting alone; indeed, they inhibit the function of neutrophils, platelets, macrophages and mast cells. The most potent proinflammatory agent yet identified as a product of arachidonate is LTB4. LTB4 is a potent Ca ionophore, a strong chemo-attractant, induces local inflammation, and activates neutrophils.

Arthritis, Rheumatoid↗
PubMed1990

Differential effects of lithocholate on rat neutrophil activation.

Neutrophils (PMNs) may be exposed to high concentrations of biliary products during cholestasis and other hepatic disorders. We have previously reported that bile and certain bile salts enhance superoxide (O2-) release from neutrophils activated with phorbol myristate acetate (PMA) (Dahm et al.: Toxicol. Appl. Pharmacol. 95, 82, 1988), suggesting that PMN oxidative metabolism might be altered in toxicoses or disease states characterized by elevations in serum bile salts and other biliary products. In the present study, we characterized the priming effect of lithocholate for O2- release and also examined the effects of lithocholate on enzyme release from PMNs. PMNs preincubated with lithocholate at concentrations which did not directly stimulate O2- release (3-100 microM) and activated with PMA released greater amounts of O2- than controls exposed to PMA alone, illustrating a priming effect. O2- release from lithocholate-primed PMNs rose sharply between 5 and 10 min after PMA addition and then ceased between 10 and 30 min. The priming effect of lithocholate toward PMA-activated PMNs was reduced approximately 50% by washing PMNs after lithocholate addition and was not dependent on extracellular Ca2+, although removal of Ca2+ from the incubation buffer enhanced the cytotoxicity of lithocholate toward PMNs. In Ca2(+)-supplemented medium, lithocholate primed PMNs for O2- release when formyl-methionyl-leucyl-phenylalanine (FMLP, 10(-8)-10(-6) M) or calcium ionophore, A23187 (10(-7) or 10(-6)M), was used to activate PMNs. Lithocholate (100 microM) by itself had only marginal effects on release of lysozyme or beta-glucuronidase from PMNs. However, lithocholate (100 microM) inhibited beta-glucuronidase release from FMLP-stimulated PMNs to near-baseline levels. When FMLP was added to PMNs prior to lithocholate, beta-glucuronidase release was not reduced as it was when the order of addition was the reverse. Lithocholate had no effect on PMA-stimulated lysozyme release. These results indicate that lithocholate has different actions on PMN O2- release and enzyme release and suggest that lithocholate might exert its action on the PMN plasma membrane.

Animals↗
PubMed1992

Activated neutrophils impair rabbit heart recovery after hypothermic global ischemia.

Cardiopulmonary bypass is known to cause neutrophil activation, and activated neutrophils appear to be of importance in myocardial reperfusion injury. This study examined the effect of a preischemic infusion of activated neutrophils on the recovery of myocardial function after 40 minutes of hypothermic global ischemia. Studies were carried out in three groups of Langendorff-perfused rabbit hearts: control, control (unactivated) neutrophil infusion, and phorbol myristate acetate-activated neutrophil infusion. The activated neutrophil group showed significant deterioration in function during the activated neutrophil infusion. All three groups demonstrated significant depression of function initially after reperfusion, but the two control groups subsequently recovered to baseline levels. The activated neutrophil group, however, showed a persistent significant depression in ventricular force, rate of ventricular tension development, and rate of ventricular relaxation as well as a significant increase in coronary vascular resistance. It is concluded that activated neutrophils depress myocardial function and contribute to impaired recovery of function after global hypothermic ischemia.

Animals↗
PubMed1991

Neutrophil-activating peptide 2 and gro/melanoma growth-stimulatory activity interact with neutrophil-activating peptide 1/interleukin 8 receptors on human neutrophils.

Neutrophil-activating peptide 1/interleukin 8 (NAP-1/IL-8), neutrophil-activating peptide 2 (NAP-2), and gro/melanoma growth-stimulatory activity (gro/MGSA) are potent inflammatory cytokines with homologous structure and similar neutrophil-activating properties. Receptors on human neutrophils that interact with these peptides were studied. Analysis of 125I-NAP-1/IL-8 binding at 0-4 degrees C revealed 64,500 +/- 14,000 receptors/cell with an apparent Kd of 0.18 +/- 0.07 nM (mean +/- S.D. of six independent experiments). Unlabeled NAP-1/IL-8, NAP-2, and gro/MGSA competed with 125I-NAP-1/IL-8 for binding to human neutrophils. Competition with increasing concentrations of unlabeled NAP-2 and gro/MGSA resolved two classes of NAP-1/IL-8 binding sites: about 70% of them bound NAP-2 and gro/MGSA with high affinity (Kd: 0.34 +/- 0.2 and 0.14 +/- 0.02), while 30% were of low affinity (Kd: 100 +/- 20 and 130 +/- 10 nM). Different binding sites, however, were not apparent upon competition with unlabeled NAP-1/IL-8, suggesting that both classes of receptors have similar affinities for NAP-1/IL-8. The existence of two receptors was also suggested by ligand cross-linking and cross-desensitization experiments. Two neutrophil membrane proteins with apparent Mr of 66,000-74,000 and 42,000-46,000 became cross-linked to 125I-NAP-1/IL-8, and the labeling was decreased when excess NAP-1/IL-8, NAP-2, or gro/MGSA was present. Stimulation of neutrophils with NAP-1/IL-8 resulted in desensitization toward a subsequent challenge with NAP-2 or gro/MGSA as shown by the rise in cytosolic free calcium. By contrast, following primary stimulation with NAP-2 or gro/MGSA, responses to NAP-1/IL-8 were only moderately attenuated, supporting the existence of NAP-1/IL-8 receptors which bind NAP-2 or gro/MGSA with low affinity. In conclusion, our results demonstrate that NAP-2 and gro/MGSA act upon human neutrophils by directly interacting with two classes of receptors for NAP-1/IL-8.

Amino Acid Sequence↗
PubMed1999

Plaunotol prevents indomethacin-induced gastric mucosal injury in rats by inhibiting neutrophil activation.

BACKGROUND: Activated neutrophils play a critical role in indomethacin-induced gastric mucosal injury. AIM: To investigate the effect of plaunotol, an anti-ulcer agent, on neutrophil activation in vitro and its effect on gastric mucosal injury and gastric accumulation of neutrophils in rats given indomethacin. METHODS: Human monocytes and neutrophils were isolated from the peripheral blood of healthy volunteers. We examined the effect of plaunotol on neutrophil elastase release, production of O2-, intracellular calcium concentration and expression of adhesion molecules CD11b and CD18 in activated neutrophils in vitro. The effect of plaunotol on TNF-alpha production by monocytes stimulated with endotoxin also was investigated in vitro. The effect of plaunotol (100 mg/kg, p.o.) on gastric mucosal injury and neutrophil accumulation was investigated in male Wistar rats given indomethacin (30 mg/kg, p.o.). RESULTS: Plaunotol inhibited the fMLP-induced release of neutrophil elastase from activated neutrophils, as well as the opsonized zymosan-induced production of O2- by neutrophils. Plaunotol significantly inhibited increased levels of intracellular calcium, a second messenger of neutrophil activation, in vitro. The fMLP-induced increases in CD11b and CD18 expression were also inhibited by plaunotol in vitro. Plaunotol inhibited monocytic production of TNF-alpha, a potent activator of neutrophils. Both gastric mucosal injury and gastric neutrophil infiltration in rats given indomethacin were significantly inhibited by the oral administration of plaunotol. CONCLUSIONS: Plaunotol inhibits indomethacin-induced gastric mucosal injury, at least in part by inhibiting neutrophil activation.

Animals↗
PubMed2005

Neutrophils activation can be diminished by apolipoprotein A-I.

High density lipoprotein (HDL) has anti-inflammatory function. To investigate the effects of apolipoprotein A-I (ApoA-I), the major apolipoprotein of HDL, on activated neutrophils, we stimulated neutrophils in vitro with fMLP and PMA, as a receptor-binding and a nonreceptor-binding stimuli, respectively, and incubated ApoA-I with those neutrophils. Three conditions were utilized: 1) resting neutrophils + ApoA-I (0, 2.5,5, 10 microg/mL respectively), 2) fMLP(10(-7) mol/L)-activated neutrophils + ApoA-I (0, 2.5, 5, 10 microg/mL respectively), and 3) PMA(10(-7) mol/L)-activated neutrophils + ApoA-I (0, 2.5, 5, 10 microg/mL respectively). After incubation, we measured neutrophils adhesion to fibronectin, oxidative bust (O2- and H2O2 production), degranulation (release of MPO and elastase), and L929 cell mortality which were attacked by release-out of cytokines in activated neutrophils (using MTT). Our results showed that in vitro ApoA-I inhibits fMLP- and PMA- activated neutrophil adhesion, oxidative burst, degranulation and L929 cell mortality. These inhibition effects of ApoA-I on fMLP-activated neutrophils are more powerful than that on PMA-activated neutrophils. ApoA-I has no effect on resting neutrophils. We concluded that ApoA-I could diminish the function of activated neutrophils.

Acute-Phase Reaction↗
PubMed1992

Activation of complement in normal serum by hydrogen peroxide and hydrogen peroxide-related oxygen radicals produced by activated neutrophils.

Neutrophils activated by soluble particulate stimuli generate superoxide anion and subsequently form hydrogen peroxide and other oxygen radicals. The effect of hydrogen peroxide on the complement system in normal serum was investigated. Treatment of normal serum with hydrogen peroxide resulted in a diminution of the haemolytic activity of the total and alternative complement pathways and the haemolytic titres of C3 and C5 but not of C2, in normal serum. These decreases in complement activity depended on the concentration of hydrogen peroxide added to the serum. Immunoelectrophoretic analysis of hydrogen peroxide-treated serum showed that C3 and C5 proteins were activated. Complement degradation products C3a and C5a were produced in normal serum treated with hydrogen peroxide, and 20 mM EDTA abolished C3a and C5a production in hydrogen peroxide-treated serum but 20 mM Mg-EGTA did not. Catalase completely abolished and dimethylsulphoxide and D-mannitol, hydroxyl radical scavengers, partially inhibited the hydrogen peroxide-mediated complement activation. Hypochlorite, incubated with normal serum, significantly inhibited serum haemolytic activity, and sodium thiosulphate, a reducing agent, abolished the effect of hypochlorite. Normal serum incubated with activated neutrophils showed neutrophil chemotactic activity and decreased serum haemolytic activity, and the addition of catalase or methionine (5 mM) completely abolished the effects of activated neutrophils. These results suggest that hydrogen peroxide activates complement via an alternative pathway of complement activation and that hydroxyl radicals and other hydrogen peroxide-related species such as hypochlorite are most likely involved in hydrogen peroxide-mediated complement activation. Complement activation by oxygen radicals produced by activated neutrophils may be one of the mechanisms by which complement is activated in human immune complex diseases.

Complement Activation↗
PubMedDate not supplied

Relocalization of endothelial cell beta-catenin after coculture with activated neutrophils from patients undergoing cardiac surgery with cardiopulmonary bypass.

Cardiac surgery with cardiopulmonary bypass (CPB) is associated with neutrophil activation, inflammation, and consecutive edema. The impairment of endothelial junction molecules, and thus, hyperpermeability elicited by the interaction of activated neutrophils with endothelial cells may be important in this regard. Cocultures with human endothelial cells and neutrophils from 10 cardiac surgery patients with CPB were used to evaluate the role of neutrophils in modifications of the endothelial zonula adherens molecules VE-cadherin and beta-catenin. Laser scan microscopic analyses showed that neutrophils, which were isolated after the beginning of CPB, significantly impaired intracellular redistribution of endothelial beta-catenin with regard to membrane association (p <.0002) and staining pattern (p <.0001). VE-cadherin localization was not found to be significantly modified. Western blots with total cell extracts showed that amounts of beta-catenin did not vary significantly after co-culture with activated neutrophils. Activated neutrophils during cardiac surgery with CPB may induce endothelial dysfunction by impairing beta-catenin localization and thus contribute to endothelial hyperpermeability.

Antigens, CD↗
PubMed1991

Membrane surface antigen expression on neutrophils: a reappraisal of the use of surface markers for neutrophil activation.

Neutrophil research relies largely on studies with highly purified cells. Yet the isolation procedures induce changes in surface expression of several proteins. We used a large panel of monoclonal antibodies (MoAbs) to characterize in detail the phenotypic changes during isolation and stimulation of human neutrophils. Centrifugation on density gradients appears to be the crucial step that causes an increase in expression of antigens not detectable on neutrophils in whole blood samples (cytochrome b558 recognized by MoAb 7D5; and CD10) or expressed at significantly lower levels (CD11a, CD11b, CD11c, CD13, CD16, CD45, and CD67). Other antigens were unaffected by the density gradient centrifugation step (CD32, CD54, CD58, Leu-8, HLA class I). Upregulation of antigens was also determined by stimulation of purified neutrophils. Upregulation of CD63 was an excellent marker for release from azurophil granules. We subsequently related the surface antigen expression to functional activities of purified neutrophils. From these experiments, we concluded that 7D5-as "early activation" marker--does not necessarily discriminate between primed or resting neutrophils with respect to NADPH oxidase activity.

Antibodies, Monoclonal↗
PubMed2000

Inhibition of neutrophil activation by ranitidine contributes to prevent stress-induced gastric mucosal injury in rats.

OBJECTIVE: Activated neutrophils play a critical role in stress-induced gastric mucosal injury. We investigated the effect of ranitidine, an H2-receptor antagonist, on neutrophil activation in vitro and in rats with stress-induced gastric mucosal injury. DESIGN: Prospective, randomized, blinded, controlled study. SETTING: Research laboratory at a university medical center. INTERVENTIONS: Effects of ranitidine on neutrophil elastase release, production of O2-, intracellular calcium concentration and expression of adhesion molecules CD11b and CD18 were examined in human neutrophils in vitro. The effect of ranitidine (30 mg/kg iv) on the development of gastric mucosal injury, neutrophil accumulation, and lipid peroxidation was investigated in male Wistar rats subjected to water-immersion restraint stress. MEASUREMENTS AND MAIN RESULTS: Ranitidine inhibited the release of neutrophil elastase as well as the production of O2-, the increase in the concentrations of intracellular calcium, a second messenger of neutrophil activation, and increases in CD11b and CD18 expression, in activated neutrophils. Ranitidine did not affect the expression of E-selectin on endothelial cells in vitro. Ranitidine significantly inhibited gastric accumulation of neutrophils and gastric mucosal lipid peroxidation in rats subjected to stress. Although oral administration of acid reversed the preventive effect of pirenzepine, an anti-cholinergic drug that inhibits gastric acid secretion, it did not affect the preventive effect of ranitidine. Leukocytopenia produced effects similar to those of ranitidine in animals subjected to stress. CONCLUSIONS: Inhibition of neutrophil activation and gastric acid secretion by ranitidine might contribute to reduce stress-induced gastric mucosal injury.

Animals↗
PubMed1994

Free fatty acids enhance hypochlorous acid production by activated neutrophils.

Activated polymorphonuclear neutrophils (PMNs) may contribute to the genesis of chronic obstructive lung disease in long-term cigarette smokers. However, it is not presently known which elements in smoke are important in triggering this progressive pulmonary damage or in affecting the activities of inflammatory cells such as PMNS. We earlier found substances in organic concentrates of cigarette smoke that bound ferrous iron and transferred the metal into organic phases. These substances were later identified as saturated free fatty acids, predominantly palmitic and stearic acids (16:0 and 18:0). We now report investigations of the effects of fatty acids on the oxidative metabolism of PMNs. In accord with most earlier reports, we find that saturated fatty acids have little direct effect on PMN oxidative metabolism. However, micromolar amounts of free fatty acids will more than double production of hypochlorous acid (HOCl) by PMNs stimulated with small amounts of phorbol myristate acetate. Similar fatty acid-mediated increases in HOCl production also occur when PMNs are stimulated with 1,2-dioctanoyl-sn-glycerol and 1-oleoyl-2-acetyl-sn-glycerol (also thought to be agonists of protein kinase C) but not when cells are stimulated with the calcium ionophore A23187, the formylated tripeptide f-met-leu-phe, or opsonized zymosan. Fatty acid-mediated enhancement of PMN HOCl production evidently arises from increased release of myeloperoxidase from stimulated PMNs. Furthermore, in the presence of free fatty acids, stimulated PMNs are much more cytotoxic toward cultured mink lung epithelial cells, a toxicity that is blocked by scavengers of HOCl. These results suggest that the relatively large amounts of free fatty acids present in tobacco smoke may act to amplify PMN-mediated oxidative damage to the lungs of smokers.

Adult↗
PubMed1993

Molecular characterization of receptors for human interleukin-8, GRO/melanoma growth-stimulatory activity and neutrophil activating peptide-2.

Interleukin-8 (IL-8), neutrophil activating peptide-2 (NAP-2), and growth regulated gene (GRO, also known as melanoma growth stimulatory activity) are members of a family of peptides which are chemotactic agents for inflammatory cells such as neutrophils. Receptors have been identified for IL-8, GRO and NAP-2 on human neutrophils and granulocytic cell lines, and it has been observed that these cytokines can cross-compete for binding to a common receptor. Using the recently characterized rabbit IL-8 receptor as a probe, two classes of cDNAs, termed type 1 and type 2, were isolated from a human neutrophil library. The type 1 receptor binds only IL-8 while the type 2 receptor binds IL-8, GRO and NAP-2 at high affinity when respective cDNAs are expressed in COS-7 cells. The two cDNAs encode proteins that have an amino acid sequence identity of 77% while the type 1 and 2 receptors have an identity of 84 and 74% with the rabbit IL-8 receptor. These receptors also show significant homology with receptors for other chemotactic agents and with potential coding regions from the human cytomegalovirus genome.

Amino Acid Sequence↗