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)

Peritoneal fluids obtained from mice after the intraperitoneal administration of Bordetella pertussis vaccine, heated vaccine, an extract of the organisms, killed Escherichia coli, or thioglycolate medium were examined in terms of total cells and percentage that adhered to glass cover slips during 2-h incubation period. All these substances were found to increase the number of leukocytes in peritoneal fluid within 1 to 2 days after the injection. This increase appeared to be due to an influx of macrophages and polymorphonuclear leukocytes with relative proportions at a given time dependent upon the material involved in the induction of the response. The initial increases after pertussis vaccine seemed to be due mainly to an influx of monomuclear cells, whereas with E. coli neutrophils constituted the major portion of the cell population. The percentage of peritoneal cells that attached to glass was also found to be markedly reduced in preparations obtained from mice after the injection of B. pertussis or E. coli. There appeared to be differences in persistence of this phenomenon, with preparations containing the histamine-sensitizing factor being the most active in affecting adherence properties. Thus these data would suggest that the action of B. pertussis on macrophages (or precursors) and neutrophils is not expressed in terms of suppression of emigration properties, as has been reported by others for lymphocytes, but is manifested in the alteration of glass-adherence characteristics. Within experimental limitations, it is believed that macrophages are possibly more involved in terms of altered function than are the polymorphonuclear cells.
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PMID:Characteristics of cells present in peritoneal fluids of mice injected intraperitoneally with Bordetella pertussis. 17 17

A new and sensitive assay procedure for studying erythrophagocytosis is described. The assay technique permits quantitation of the in vivo and in vitro effects of chemicals, hormones, and cell, or microbrial products, on the level of phagocytic activation of glass-adherent cells. The effect of intraperitoneal injection of BCG, Zymosan, Vitamin A, B. pertussis, cortisone, estrone, and thioglycollate on phagocytic activation of peritoneal exudate cells harvested from two days up to 28 days following drug injection was examined by this assay. Erythrophagocytosis was compared to the effect of "activated" spleen cells on tritiated thymidine uptake of a tumor target cell suspension.
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PMID:A sensitive and reproducible assay for the quantitation of erythrophagocytosis and its correlation with reduction in tritiated thymidine uptake in a tumor target cell system modified by immunoenhancing or immunosuppressive agents. 18 42

Lymphocytosis promoting factor (LPF) is a protein toxin which may have a role in the pathogenesis of pertussis. Previous results from our laboratory demonstrated that LPF inhibited random migration and chemotaxis of resident peritoneal macrophages, but had little or no effect on macrophage viability, adherence, superoxide anion release, or Fc-mediated phagocytosis. The current experiments have examined mononuclear phagocyte function in mice treated with LPF. Intravenous injection of mice with 200 ng LPF induced a prolonged monocytosis which peaked with a five-fold increase on the fifth day after injection. LPF (200 ng) also inhibited the increase in peritoneal macrophages induced by the intraperitoneal injection of either thioglycolate broth, phytohemagglutinin, or paraffin oil. The LPF-induced monocytosis on the fifth day after injections was not altered by the intraperitoneal injection of thioglycolate broth. LPF doses sufficient to induce leukocytosis (greater than or equal to 25 ng) significantly inhibited the increase in peritoneal macrophages induced by an inflammatory agent. These observed in vitro and in vivo effects of LPF were lost when LPF was subjected to treatments that eliminated its leukocytosis-promoting activity. The results indicate that coincident with an LPF-induced monocytosis is a reduction in the number of macrophages at a site of inflammation. An in vivo inhibition of mononuclear phagocyte migration would explain both of these effects of LPF, and is consistent with the in vitro inhibition of macrophage migration. The results suggest that a possible role for LPF in pathogenesis is the inhibition of macrophage migration to the site of Bordetella pertussis infection.
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PMID:Altered mononuclear phagocyte function in mice treated with the lymphocytosis promoting factor of Bordetella pertussis. 287 33

Changes were observed in the DNA-synthesising cells of the murine peritoneal cavity after a single subcutaneous injection of (1) fluid thioglycollate medium, (2) guinea-pig serum, (3) pertussis vaccine, (4) fresh egg albumen, (5) bovine albumin Fraction 5, (6) normal saline as control. The subcutaneous route was chosen in order to avoid direct peritoneal irritation. A total of 180 animals was employed, in six groups of 30 each, and in each group five animals per day were examined for six days. In all cases except the controls there was a significant increase in the number of DNA-synthesising cells in the peritoneal fluid, as measured in autoradiographs following incubation with tritiated thymidine. The labelled cells were predominantly lymphoid, some resembling the transitional cells of bone marrow. There was also a smaller number of labelled macrophages. Changes were maximal after thioglycollate. The peak percentage of labelled cells occurred on Day 1 after thioglycollate and egg albumen, on Day 2 after guinea-pig serum, and on Day 4 after pertussis vaccine and bovine albumin.
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PMID:DNA synthesis in peritoneal lymphoid cells. Indirect induction of changes. 406 83

Previous results from our laboratory demonstrated that purified lymphocytosis-promoting factor (LPF), a protein toxin from Bordetella pertussis, inhibited the migration of murine macrophages in vitro. The current study examined the in vivo effects of LPF on mononuclear phagocyte circulation and response to an inflammatory stimulus. Intravenous injection of mice with 200 ng of LPF produced a prolonged monocytosis which peaked with a fivefold increase on day 5 after injection. LPF (200 ng) also inhibited by more than 75% the increase in peritoneal inflammatory macrophages induced by intraperitoneal injection of thioglycolate broth, phytohemagglutinin, or paraffin oil. The inhibition was significant when thioglycolate was given 1 h or 2 or 4 days after LPF but not when thioglycolate was given 2 or 4 days before LPF. The LPF-induced monocytosis on day 5 after injections was not altered by the intraperitoneal injection of thioglycolate broth. The leukocytosis-promoting and macrophage-inhibiting properties of LPF were the same in N:NIH(S) and C3H/HeJ mice. Treatments of LPF that reduced the leukocytosis-promoting effect of LPF also reduced the ability of LPF to inhibit the macrophage response. LPF doses sufficient to induce leukocytosis (greater than or equal to 25 ng) significantly inhibited the thioglycolate-induced increase in peritoneal macrophages. The results indicate that coincident with an LPF-induced monocytosis is a reduction in the number of mononuclear phagocytes at a site of inflammation. An in vivo inhibition of mononuclear phagocyte migration would explain both effects of LPF and is consistent with the in vitro inhibition of macrophage migration by LPF.
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PMID:Lymphocytosis-promoting factor of Bordetella pertussis alters mononuclear phagocyte circulation and response to inflammation. 609 57

C57BL/6 mice were subjected to a full thickness scald thermal injury covering 25% of their total body surface area, and thioglycollate elicited peritoneal macrophages (Mphi were isolated 4 days later. Mphi from injured mice produced significantly greater amounts of reactive nitrogen intermediates and tumor necrosis factor-alpha in response to lipopolysaccharide and lipid A. Pertussis toxin (PTX) treatment of Mphi dose-dependently inhibited reactive nitrogen intermediate production in Mphi from sham-treated mice; however, Mphi from injured mice were insensitive to PTX-mediated inhibition. Conversely, tumor necrosis factor-alpha production was enhanced by PTX treatment, with Mphi from injured mice being more sensitive than Mphi from sham-treated mice to this effect of PTX. These results indicate that thermal injury increases Mphi sensitivity to lipopolysaccharide by a mechanism that is both PTX sensitive and PTX insensitive, thereby suggesting a role for G proteins in the modulation of Mphi activity after thermal injury.
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PMID:Thermal injury induces macrophage hyperactivity through pertussis toxin-sensitive and -insensitive pathways. 956 52

Galpha15 activates phospholipase Cbeta in response to the greatest variety of agonist-stimulated heptahelical receptors among the four Gq class G-protein alpha subunits expressed in mammals. Galpha15 is primarily expressed in hematopoietic cells in fetal and adult mice. We disrupted the Galpha15 gene by homologous recombination in embryonic stem cells to identify its biological functions. Surprisingly, hematopoiesis was normal in Galpha15(-/-) mice, Galpha15(-/-) Galphaq(-/-) double-knockout mice (which express only Galpha11 in most hematopoietic cells), and Galpha11(-/-) mice, suggesting functional redundancy in Gq class signaling. Inflammatory challenges, including thioglycolate-induced peritonitis and infection with Trichinella spiralis, stimulated similar responses in Galpha15(-/-) adults and wild-type siblings. Agonist-stimulated Ca(2+) release from intracellular stores was assayed to identify signaling defects in primary cultures of thioglycolate-elicited macrophages isolated from Galpha15(-/-) mice. C5a-stimulated phosphoinositide accumulation and Ca(2+) release was significantly reduced in Galpha15(-/-) macrophages. Ca(2+) signaling was abolished only in mutant cells pretreated with pertussis toxin, suggesting that the C5a receptor couples to both Galpha15 and Galphai in vivo. Signaling evoked by other receptors coupled by Gq class alpha subunits appeared normal in Galpha15(-/-) macrophages. Despite discrete signaling defects, compensation by coexpressed Gq and/or Gi class alpha subunits may suppress abnormalities in Galpha15-deficient mice.
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PMID:Normal hematopoiesis and inflammatory responses despite discrete signaling defects in Galpha15 knockout mice. 1062 36

Although class A type I/II scavenger receptor (SR-A) is involved in numerous macrophage functions, its signaling ability remains uncertain. We used monoclonal antibodies (mAb) to specifically stimulate receptors on mouse alveolar (AMs) and peritoneal macrophages (PMs). Immobilized anti-SR-A (2F8) and anti-FcgammaR II/III (2.4G2) mAb stimulated hydrogen peroxide (H2O2) production in normal C3H/HeJ AMs (by 55% and 98%, respectively) and resident PMs (66% and 128%). The 2F8 mAb-stimulated H2O2 production resulted from specific stimulation of SR-A, since this response was absent in AMs from SR-A-deficient or C57BL/6 mice--the latter strain expressing an allelic form of SR-A, unrecognizable by 2F8 mAb. H2O2 production stimulated by anti-SR-A but not by anti-FcgammaRII/III mAb was preserved in FcgammaRI/III-deficient mice, ruling out involvement of FcgammaRs in the 2F8 mAb effect. In comparison with the FcgammaR-stimulated respiratory burst, the response to anti-SR-A mAb was delayed and, unlike the former, inhibited by pertussis toxin. Ligation of SR-A also inhibited lipopolysaccharide plus interferon-gamma-stimulated interleukin-12 (IL-12) release, by 25% in AMs and by 68% in thioglycollate-elicited PMs, consistent with different levels of SR-A expression. Neither nitrite nor IL-6 accumulation was affected by anti-SR-A mAb. SR-A-stimulated H2O2 does not seem to mediate the inhibition of IL-12 release, since the inhibition was neither reversed by scavenging of H2O2 nor mimicked by exogenous H2O2. Our results indicate that SR-A not only mediates endocytosis but can also generate signals such as H2O2, which may affect microbicidal or proinflammatory functions.
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PMID:Scavenger receptor A mediates H2O2 production and suppression of IL-12 release in murine macrophages. 1531 30

The signaling events leading to the activation of integrins and firm arrest of rolling neutrophils in inflamed venules have yet to be elucidated. In vitro assays suggest that both E-selectin and chemokines can trigger arrest of rolling neutrophils, but E-selectin(-/-) mice have normal levels of adherent neutrophils in inflamed venules. To test whether chemokine-induced neutrophil arrest in vivo can be unmasked by blocking E-selectin, we investigated neutrophil adhesion in inflamed cremaster muscle venules in tumor necrosis factor (TNF)-alpha-treated CXCR2(-/-) or wild-type (WT) mice injected with E-selectin blocking monoclonal antibody (mAb) 9A9. To block chemokine receptor signaling, we investigated E-selectin(-/-) or WT mice treated with pertussis toxin (PTx) intravenously. Neutrophil adhesion was unchanged in CXCR2(-/-), E-selectin(-/-), PTx-treated WT, or mAb 9A9-treated WT mice. However, TNF-alpha-induced neutrophil adhesion was almost completely abrogated in E-selectin(-/-) mice treated with PTx and significantly reduced in CXCR2(-/-) mice treated with the E-selectin blocking mAb. In thioglycollate-induced peritonitis, PTx treatment blocked neutrophil recruitment into the peritoneum of E-selectin(-/-) mice, but had only a partial effect in WT animals. These data show that E-selectin- and chemokine-mediated arrest mechanisms are overlapping in this model and identify CXCR2 as an important neutrophil arrest chemokine in vivo.
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PMID:CXCR2- and E-selectin-induced neutrophil arrest during inflammation in vivo. 1546 24

Engagement of neutrophils by E-selectin results in integrin activation. Here, we investigated primary mouse neutrophils in whole blood by using intravital microscopy and autoperfused flow chambers. Slow rolling on E-selectin coimmobilized with intercellular adhesion molecule-1 (ICAM-1) required P-selectin glycoprotein ligand (PSGL)-1, was dependent on alpha(L)beta(2) integrin (LFA-1), and required continuous E-selectin engagement. Slow rolling was abolished by pharmacological blockade of spleen tyrosine kinase (Syk) and was absent in Syk(-/-) bone-marrow chimeric mice. Treatment with tumor necrosis factor-alpha lowered rolling velocity further and induced CXC chemokine ligand-1 (CXCL1) and CXC chemokine receptor-2 (CXCR2)-dependent leukocyte arrest on E-selectin and ICAM-1. Arrest but not rolling was blocked by an allosteric inhibitor of LFA-1 activation. Neutrophil recruitment in a thioglycollate-induced peritonitis model was almost completely inhibited in Selplg(-/-) mice or Syk(-/-) bone-marrow chimeras treated with pertussis toxin. This identifies a second neutrophil-activation pathway that is as important as activation through G protein-coupled receptors (GPCRs).
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PMID:Spleen tyrosine kinase Syk is necessary for E-selectin-induced alpha(L)beta(2) integrin-mediated rolling on intercellular adhesion molecule-1. 1754 54


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