Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of the neuropeptides substance P, neurokinin A and alpha-calcitonin gene-related peptide (CGRP) on human neutrophil granulocytes was investigated. Substance P induced secondary granule secretion at a concentration of 100 microM. CGRP induced a significant secretory response at 10 microM and thus appeared to be about 10 times more potent than substance P. Calcitonin and a fragment of CGRP, CGRP(8-37), had no effect on neutrophil degranulation. The chemotactic peptide antagonist BOC-MLP (100 microM) inhibited lactoferrin secretion mediated both by CGRP and chemotactic peptide FMLP almost completely, while secretion in response to tumour necrosis factor (TNF) was unaffected. Results from receptor binding studies showed that CGRP and N-formyl-methionyl-leucyl-phenylalanine (FMLP) do not compete for binding. This indicates that CGRP does not exert its effects by binding to the chemotactic peptide receptor. CGRP induced a rapid increase in the cytosolic-free calcium concentration and this increase was not, unlike that induced by FMLP, abolished by preincubation of the cells with pertussis toxin (1000 ng/ml). Therefore CGRP signal transduction in neutrophils appears to involve rapid changes in the cytosolic-free calcium concentration but not a pertussis toxin-sensitive G-protein. In summary, this is the first report to show that CGRP can directly activate neutrophil granulocytes, and this probably occurs via a cell surface receptor which is distinct from that of FMLP although both the CGRP and FMLP-mediated effects can be blocked by BOC-MLP.
 ...
PMID:Calcitonin gene-related peptide (CGRP) activates human neutrophils--inhibition by chemotactic peptide antagonist BOC-MLP. 128 94

Bordetella pertussis was grown in iron (Fe)-free defined medium to limit the growth of the organism. Doubling times of the Fe-starved organism increased by approximately 1 h, and a 40% reduction in the final extent of growth in Fe-depleted medium was observed. Under these conditions, a hydroxamate siderophore named bordetellin was secreted by B. pertussis. Lactoferrin and transferrin supported growth of B. pertussis even when the protein was sequestered inside dialysis tubing. This suggested that binding of lactoferrin and transferrin to B. pertussis was not essential and that bordetellin production plays a major role in Fe uptake. Solid-phase dot blot assays indicated weak binding of lactoferrin to the cell surface, consistent with previous reports of a lactoferrin receptor. Three new proteins of 97, 77, and 63 kDa were synthesized in response to Fe starvation. Fe-inducible proteins of 103, 72, 24, 21, and 18 kDa were also observed. The synthesis of lipopolysaccharide was also altered by Fe availability.
 ...
PMID:Siderophore production and membrane alterations by Bordetella pertussis in response to iron starvation. 130 10

Bordetella pertussis and Bordetella bronchiseptica were both able to grow in iron-deficient medium when supplemented with iron-saturated human lactoferrin or transferrin but not with human apotransferrin. Direct contact between the transferrins and the Bordetella cells did not appear to be required for growth but considerably improved the growth of the organisms. Analysis of B. pertussis and B. bronchiseptica whole-cell lysates from cultures carried out in iron-deficient or iron-replete media revealed iron-repressible proteins (IRPs) of 27 kDa in B. pertussis and of 30, 32, 73.5, and 79.5 kDa in B. bronchiseptica. Iron-inducible proteins of 16, 23.5, 36.5, and 92.5 kDa and of 17, 23.5, 70, 84, and 91 kDa were also identified in B. pertussis and B. bronchiseptica, respectively. By use of affinity chromatography with iron-saturated human lactoferrin or transferrin as ligands, the 27- and 32-kDa IRPs from B. pertussis and B. bronchiseptica, respectively, were specifically isolated. By using iron-chelated affinity columns, we showed that these proteins exhibit an affinity for iron. Cell fractionation experiments indicated that both of these proteins are probably associated with the outer membrane. Growth of the organisms under modulating conditions showed that the production of these IRPs is not under the genetic transcriptional control of vir or bvg, the general virulence regulon in Bordetella spp.
 ...
PMID:Identification and purification of transferrin- and lactoferrin-binding proteins of Bordetella pertussis and Bordetella bronchiseptica. 193 57

In the absence of serum, nonpiliated gonococci expressing PII outer membrane proteins (PIIs) adhere to human neutrophils whereas non-PII-expressing (PII-) gonococci do not. After an observation that neutrophils in monolayers bound more gonococci than neutrophils in suspension, we treated neutrophil suspensions with known stimulants of degranulation and measured subsequent gonococcal adherence to suspended neutrophils. The chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fmlp), the potent secretagogue phorbol myristate acetate, and the calcium ionophore A23187 all caused increased adherence of PII+ gonococci, but not PII- gonococci, to neutrophils in a dose-responsive manner. Increased adherence of gonococci to neutrophils was paralleled by increased degranulation of neutrophil myeloperoxidase, lysozyme, and lactoferrin. Inhibition of fmlp-induced neutrophil degranulation by pertussis toxin, the calmodulin inhibitors trifluoperazine and N-5-chloronaphthalene sulfonamide, or the intracellular calcium-binding agent trimethoxybenzoic acid also inhibited fmlp-induced gonococcal adherence to neutrophils. Neither undifferentiated nor myelocytically differentiated HL-60 cells, which possess primary but defective or nonexistent secondary granules, bound PII+ or PII- gonococci. Gonococci did not adhere to human monocytes, monocyte-derived macrophages, lymphocytes, platelets, or erythrocytes, indicating that several receptors, such as the complement receptors CR1, CR3 (CD11b/CD18), and CR4 (CD11c/CD18) or the adherence complex LFA-1 (CD11a/CD18), were probably not involved in gonococcal adherence to human neutrophils.
 ...
PMID:Up-regulation of human neutrophil receptors for Neisseria gonorrhoeae expressing PII outer membrane proteins. 211 69

Lymphotoxin (LT) can activate human neutrophils. Using a hemolytic plaque assay to detect secretion of lactoferrin and myeloperoxidase (MPO) from single adherent neutrophils, we showed that LT induced secretion from both primary and secondary granules. Incubation of cells with cytochalasin B was required for MPO secretion, and it enhanced lactoferrin secretion. Pertussis toxin, which blocks a G-protein in the plasma membrane, inhibited LT-induced exocytosis of MPO, but not of lactoferrin. Incubation with LT did not induce any detectable changes of the cytoplasmic free [Ca2+] in neutrophils. On the other hand, secretion of granule proteins from adherent neutrophils in response to LT was blocked by loading neutrophils with quin-2 in order to increase the intracellular calcium buffering capacity. This was achieved at a concentration of quin-2, at which the secretion induced by the phorbol ester PMA and the chemotactic peptide FMLP was unaffected. Trifluoroperazine (TFP), a dual protein kinase C and calmodulin inhibitor, significantly inhibited the LT-mediated secretion of lactoferrin from adherent granulocytes. The PMA effect was unaltered by TFP under these conditions, suggesting that the inhibitory effect was on a calcium-calmodulin dependent step. The secretion induced by TNF and GM-CSF was also blocked by buffering changes in the intracellular [Ca2+] and inhibited to a similar extent by TFP. Our results suggest that calmodulin and minute changes in the cytoplasmic free [Ca2+] may be involved in a common signal transduction pathway engaged in activation of adherent neutrophils by several cytokines.
 ...
PMID:Lymphotoxin induces secretion of granule proteins from adherent neutrophils: possible role of intracellular free calcium. 216 92

Both TNF and and granulocyte/macrophage CSF (GM-CSF) can activate neutrophils. The aim of this work was to determine the effect of these cytokines on neutrophil degranulation. The secretion of lactoferrin of secondary granules and myeloperoxidase (MPO) of primary granules from single adherent human neutrophils was assayed by use of a reverse hemolytic plaque assay. Both rTNF and rGM-CSF caused secretion of lactoferrin in a dose-dependent manner. Both agents also caused secretion of MPO, but only in the presence of cytochalasin B. Preincubation with pertussis toxin inhibited rGM-CSF-induced secretion of both lactoferrin and MPO. rTNF-induced MPO secretion was also blocked by pertussis toxin, whereas lactoferrin secretion was only slightly affected. Neither rTNF nor rGM-CSF caused any detectable changes in the concentration of cytoplasmic free Ca2+ in fura-2-loaded cells. However, when neutrophils were loaded with increasing concentrations of quin-2 to buffer any local, not detectable, changes in the concentration of cytoplasmic Ca2+, both rTNF- and rGM-CSF-induced secretion of lactoferrin and MPO were almost totally abolished at a relatively low quin-2 concentration. These results suggest a role of a regulatory G-protein and minute local changes in the concentration of cytoplasmic Ca2+ in TNF- and GM-CSF-induced neutrophil degranulation.
 ...
PMID:Effect of tumor necrosis factor and granulocyte/macrophage colony-stimulating factor on neutrophil degranulation. 265 22

Bordetella pertussis was able to grow in vitro under conditions where the only iron present was bound to the iron-binding proteins ovotransferrin, transferrin or lactoferrin. Under these conditions the bacteria produced neither hydroxamate nor phenolate-catecholate siderophores to assist in the procurement of iron. Examination of B. pertussis outer-membrane preparations by SDS-PAGE and immunoblotting showed that the iron-binding protein ovotransferrin was bound directly to the bacterial surface. Assays of the binding of radiolabelled transferrin by the bacteria showed that the association was a specific process and that there was turnover of the bound proteins. Competitive binding assays indicated that lactoferrin could be bound in the same way. It is suggested that B. pertussis obtains iron directly from host iron-binding proteins during infection.
 ...
PMID:Interaction of lactoferrin and transferrins with the outer membrane of Bordetella pertussis. 288 36

The effects of pertussis toxin (PT) on human neutrophil responses mediated by the 42-kDa IgG Fc R (Fc gamma R42) were compared with its effects on responses mediated by the FMLP receptor. Pre-treatment of neutrophils with PT completely inhibited FMLP stimulation of superoxide production and blocked over 95% of FMLP-stimulated degranulation. PT inhibited superoxide production stimulated by Fc gamma R42 cross-linking by 92%. In contrast, degranulation stimulated by Fc gamma R42 was only partially inhibited, with beta-glucuronidase release inhibited by 54%, lysozyme by 33%, and lactoferrin by 78%. With either stimulus, PT inhibition was maximal in the range from 1.8 to 2 micrograms/ml. Responses to both stimuli declined in a parallel fashion with increasing time of exposure to PT with maximal inhibition occurring after 2 h of exposure. Inhibition of FMLP responses and Fc gamma R42-mediated superoxide production, but not degranulation, correlated with ADP-ribosylation of a 45-kDa membrane protein. Inhibition by PT of Fc gamma R42-mediated responses was not due to a change in receptor number. These data suggest that activation of polymorphonuclear neutrophils via Fc gamma R42 proceeds through two pathways, only one of which is regulated by a PT-sensitive G protein.
 ...
PMID:Pertussis toxin inhibits human neutrophil responses mediated by the 42-kilodalton IgG Fc receptor. 296 66

Subcellular fractions were prepared from human neutrophils by sucrose density gradient centrifugation and analyzed for Gi-like proteins by pertussis toxin-catalyzed [32P]ADP-ribosylation and by immunoblotting with rabbit antiserum AS/6 which recognizes purified transducin and Gi, but not Gs or Go alpha-subunits. In resting cells, approximately equal to 60% of pertussis toxin substrate retrieved from the sucrose density gradient localized to the plasma membrane-enriched fraction, approximately equal to 35% to the specific granule-enriched fraction, and approximately equal to 5% to cytosol. The azurophil granule-enriched fraction did not contain pertussis toxin substrate. In contrast to plasma membrane, the specific granule-enriched fraction demonstrated increased AS/6 immunoreactivity of a approximately equal to 41-kDa protein relative to a approximately equal to 40-kDa protein. Within the specific granule-enriched fraction, the peak of pertussis toxin substrate detected immunochemically or by [32P]ADP-ribosylation sedimented at a lighter density (rho = 1.6 g/ml) than did lactoferrin (rho = 1.19 g/ml), suggesting that the intracellular compartment bearing pertussis toxin substrate may not be the lactoferrin containing specific granule, per se. Furthermore, in neutrophils exposed to 10(-8) M N-formylmethionylleucylphenylalanine, a weak degranulating stimulus (7% lactoferrin degranulation), there was a 31-42% decline in pertussus toxin-catalyzed [32P]ADP-ribosylation of approximately equal to 40-41-kDa proteins in the specific granule-enriched fraction accompanied by a near-quantitative increase in labeling of plasma membrane. The pool of intracellular formyl peptide receptors localized to the specific granule-enriched fraction appeared functionally coupled to a cosedimenting G-protein in experiments demonstrating modulation of high affinity N-formylmethionylleucyl[3H]phenylalanine binding by guanosine 5'-(3-O-thio)triphosphate or pertussis toxin. The data indicate that neutrophils contain a surface translocatable pool of intracellular G-protein sedimenting in the specific granule-enriched fraction and support the view that mobilization of intracellular G-protein represents a mechanism by which cells can regulate receptor activity.
 ...
PMID:Subcellular localization of Gi alpha in human neutrophils. 313 54

alpha 2-Macroglobulin (alpha 2M)-methylamine binding to macrophages appears to involve two receptors. Binding of alpha 2M-methylamine to low density lipoprotein-related protein (LRP) results in cellular uptake and degradation, while binding to a newly described alpha 2M signaling receptor elevates intracellular calcium ([Ca2+]i) and inositol phosphates. We now demonstrate that binding of lactoferrin, Pseudomonas exotoxin A, and lipoprotein lipase to LRP on macrophages results in increased [Ca2+]i and inositol 1,4,5-triphosphate. Receptor-associated protein, which binds to LRP but not the alpha 2M signaling receptor, blocks the lactoferrin signal but has no effect on alpha 2M-methylamine signaling. The latter observation supports our hypothesis that a distinct signaling receptor binds alpha 2M-methylamine. We further demonstrate that the signaling events induced by lactoferrin may involve a pertussis toxin-sensitive G protein, while the alpha 2M signaling receptor appears to be coupled to a pertussis toxin-insensitive G protein.
 ...
PMID:The relationship between low density lipoprotein-related protein/alpha 2-macroglobulin (alpha 2M) receptors and the newly described alpha 2M signaling receptor. 751 27


1 2 3 Next >>