Inheritance of Responsiveness to Pertussis HSF in Mice

Ac, Wardlaw

doi:10.1159/000230313

Cited by 36 publications

(28 citation statements)

References 14 publications

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“…These results demonstrate that the genetic control of susceptibility to vasoactive amine sensitization is vasoactive amine specific and that Bphs/Hrh1 does not play a role in controlling sensitivity to serotonin. These data help to explain some of the conflicting results in the literature with respect to differences in susceptibility to vasoactive amine sensitization elicited with histamine, serotonin, or combinations thereof among inbred strains of mice (22,28,29,42,43). Other factors that we have clearly established as confounding in our studies over the years include the purity of the PTX and the variability in classifying strains as susceptible and resistant based on vastly varying times to death as the end point.…”

Section: Resultsmentioning

confidence: 62%

“…The A subunit is an ADPribosyltransferase which affects signal transduction by ribosylation of the ␣ subunit of trimeric Gi proteins while the B oligomer binds cell surface receptors on a variety of mammalian cells (19,31). PTX, when administered in vivo, elicits a large number of physiological responses including disruption of glucose regulation, leukocytosis, adjuvant activity, increased vascular permeability associated with alteration of blood-tissue barrier functions, sensitization to vasoactive agents, and death (12,24,27,29,44).Inbred strains of mice differ in susceptibility to vasoactive amine challenge following PTX sensitization in that genetically susceptible strains die from hypotensive and hypovolemic shock whereas resistant strains do not (29,43). Bphs, the gene controlling susceptibility to PTX-induced hypersensitivity to histamine, was previously mapped to the central region of mouse chromosome 6 (39) and recently identified as being the histamine H 1 receptor (Hrh1) (25).…”

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confidence: 99%

“…Inbred strains of mice differ in susceptibility to vasoactive amine challenge following PTX sensitization in that genetically susceptible strains die from hypotensive and hypovolemic shock whereas resistant strains do not (29,43). Bphs, the gene controlling susceptibility to PTX-induced hypersensitivity to histamine, was previously mapped to the central region of mouse chromosome 6 (39) and recently identified as being the histamine H 1 receptor (Hrh1) (25).…”

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confidence: 99%

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Analysis of the Role ofBphs/Hrh1in the Genetic Control of Responsiveness to Pertussis Toxin

et al. 2003

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In vivo intoxication with Bordetella pertussis toxin (PTX) elicits a variety of physiological responses including a marked leukocytosis, disruption of glucose regulation, adjuvant activity, alterations in vascular function, hypersensitivity to vasoactive agents, and death. We recently identified Bphs, the locus controlling PTX-induced hypersensitivity to the vasoactive amine histamine, as the histamine H 1 receptor (Hrh1). In this study Bphs congenic mice and mice with a disrupted Hrh1 gene were used to examine the role of Bphs/Hrh1 in the genetic control of susceptibility to a number of phenotypes elicited following in vivo intoxication. We report that the contribution of Bphs/Hrh1 to the overall genetic control of responsiveness to PTX is restricted to susceptibility to histamine hypersensitivity and enhancement of antigen-specific delayed-type hypersensitivity responses. Furthermore, the genetic contribution of Bphs/Hrh1 to vasoactive amine sensitization is specific for histamine, since hypersensitivity to serotonin was unaffected by Bphs/Hrh1. Bphs/Hrh1 also did not significantly influence susceptibility to the lethal effects, the leukocytosis response, disruption of glucose regulation, and histamineindependent increases in vascular permeability associated with in vivo intoxication. Nevertheless, significant interstrain differences in susceptibility to the lethal effects of PTX and leukocytosis response were observed. These results indicate that the phenotypic variation in responsiveness to PTX reflects the genetic control of distinct intermediate phenotypes rather than allelic variation in genes controlling overall susceptibility to intoxication.Pertussis toxin (PTX) is a major virulence factor of Bordetella pertussis, the causative agent of whooping cough (9). The holotoxin is a hexameric protein that conforms to the A/B model of bacterial exotoxins (31). The A subunit is an ADPribosyltransferase which affects signal transduction by ribosylation of the ␣ subunit of trimeric Gi proteins while the B oligomer binds cell surface receptors on a variety of mammalian cells (19,31). PTX, when administered in vivo, elicits a large number of physiological responses including disruption of glucose regulation, leukocytosis, adjuvant activity, increased vascular permeability associated with alteration of blood-tissue barrier functions, sensitization to vasoactive agents, and death (12,24,27,29,44).Inbred strains of mice differ in susceptibility to vasoactive amine challenge following PTX sensitization in that genetically susceptible strains die from hypotensive and hypovolemic shock whereas resistant strains do not (29,43). Bphs, the gene controlling susceptibility to PTX-induced hypersensitivity to histamine, was previously mapped to the central region of mouse chromosome 6 (39) and recently identified as being the histamine H 1 receptor (Hrh1) (25). As the first step in positionally cloning Bphs, we generated a panel of interval-specific recombinant congenic lines by using marker-assisted selection to introgress the ...

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Section: Resultsmentioning

confidence: 62%

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confidence: 99%

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confidence: 99%

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Analysis of the Role ofBphs/Hrh1in the Genetic Control of Responsiveness to Pertussis Toxin

et al. 2003

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“…The fact that Bphs was reported to be controlled by a single autosomal dominant gene (36) was confirmed when we identified Hrh1 as the gene controlling Bphs (11). In order to determine the number of loci controlling Bpss and Bpbs, we generated (B10.S ϫ SJL/J) ϫ B10.S N2 backcross mice in sufficient numbers to be able to statistically evaluate by chi-square test both one-and two-locus models of genetic control.…”

Section: Resultsmentioning

confidence: 93%

G Proteins Gα_i1/3Are Critical Targets for Bordetella pertussis Toxin-Induced Vasoactive Amine Sensitization

et al. 2014

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Pertussis toxin (PTX) is an AB5-type exotoxin produced by the bacterium Bordetella pertussis, the causative agent of whooping cough. In vivo intoxication with PTX elicits a variety of immunologic and inflammatory responses, including vasoactive amine sensitization (VAAS) to histamine (HA), serotonin (5-HT), and bradykinin (BDK). Previously, by using a forward genetic approach, we identified the HA H 1 receptor (Hrh1/H 1 R) as the gene in mice that controls differential susceptibility to B. pertussis PTX-induced HA sensitization (Bphs). Here we show, by using inbred strains of mice, F 1 hybrids, and segregating populations, that, unlike Bphs, PTX-induced 5-HT sensitivity (Bpss) and BDK sensitivity (Bpbs) are recessive traits and are separately controlled by multiple loci unlinked to 5-HT and BDK receptors, respectively. Furthermore, we found that PTX sensitizes mice to HA independently of Toll-like receptor 4, a purported receptor for PTX, and that the VAAS properties of PTX are not dependent upon endothelial caveolae or endothelial nitric oxide synthase. Finally, by using mice deficient in individual G␣ i/o G-protein subunits, we demonstrate that G␣ i1 and G␣ i3 are the critical in vivo targets of ADP-ribosylation underlying VAAS elicited by PTX exposure. Infection with the bacterium Bordetella pertussis can lead to whooping cough, usually typified by paroxysomal coughing and, in severe cases, oropharyngeal tissue swelling, hypertension, pneumothorax, and long-lasting aftereffects (1). The principal active agent in B. pertussis, pertussis toxin (PTX), is an AB5-type secreted exotoxin (2-4). The A (active) subunit catalyzes the ADP-ribosylation and thereby impairment of ␣-subunit signaling in G␣ i/o -linked heterotrimeric guanine nucleotide regulatory protein (G-protein) complexes (5). This covalent modification prevents the G␣␤␥ complex from associating with G protein-coupled receptors (GPCRs) on the cell membrane (6). The B (binding) pentamer is thought to bind cell surface receptors on a variety of mammalian cells and facilitate the cellular entry of the A subunit (7). PTX elicits diverse physiological responses in vivo, including leukocytosis and altered glucose regulation (8), increased bloodbrain barrier (BBB) permeability, and systemic vasoactive sensitization (VAAS) to biogenic amines (9). PTX is also used as an ancillary adjuvant to approximate an infectious environmental influence in animal models of tissue-specific autoimmune disease (10). Genetically, one of PTX's physiological effects, VAAS to histamine (HA), is controlled by a single autosomal dominant locus (Bphs, for B. pertussis-induced HA sensitization) and has been used as an intermediate phenotype for genetic studies of organspecific autoimmune diseases (11, 12).Although several cell types have the capacity to produce HA, mast cells are thought to be a main source during tissue inflammation (13). Mast cells also produce large amounts of serotonin (5-HT) and bradykinin (BDK), which, together with HA and other lipid and glycosylated mediators, a...

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“…pertussis to sensitise has been shown to be strongly dependent on the strain of mouse under test Wardlaw, 1970), different strains were compared quantitatively for histamine sensitisation using C. parvum and Bord. pertussis separately (tables I1 and 110.…”

Section: Parvum Sensitisation To Histamine In Diflerent Mouse Strainsmentioning

confidence: 99%

Studies on the Histamine Sensitisation Produced in Mice by Corynebacterium Parvum

Adlam

1973

Journal of Medical Microbiology

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IT has been known for many years that mice treated with Bordetella pertussis vaccine not only become resistant to challenge with the living organisms but are also sensitised to pharmacological agents and to various stressing treatments. A single injection of suitably grown and killed Bord. pertussis organisms or of " histamine-sensitising factor " extracted from them produces sensitisation to histamine, serotonin, bradykinin, endotoxin, cold shock, X-rays and anaphylaxis. Recent studies suggest that these several sensitising actions of Bord. pertussis are due to a specific action at the level of the /&receptors of the adrenergic system (Kind, 1958;Fishel, Szentivanyi and Talmage, 1964;Munoz and Bergman, 1968;Arora and Sanyal, 1968; Pieroni et al., 1971), although other mechanisms may be involved (Niwa et al., 1959;Shayer and Ganley, 1961;Gulbenkian et al., 1968).We have shown recently that killed suspensions of Corynebacterium parvum, a Gram-positive anaerobic organism unrelated to Bord. pertussis but known to possess marked lympho-reticular stimulatory properties (Halpern et al., 1964), are capable of protecting mice from challenge by mouse-virulent Bord. pertussis (Adlam, Broughton and Scott, 1972). In addition, mice treated with C. parvum or closely related diphtheroid species are sensitised to challenge with histamine (Adlam and Scott, 1973).The purpose of the present work was to compare further the sensitising properties of C. parvum and Bord. pertussis with a view to determining whether the same mechanism is involved. MATERIALS AND METHODS Bacteria.The strain of C. parvum used (Wellcome Number CN6134) was originally supplied by Professor M. Raynaud of the Pasteur Institute. Organisms were grown, harvested, killed and dry weights were determined as previously described (Adlam and Scott).The taxonomic position of C. purvum and related diphtheroids has recently been the subject of considerable controversy. Strain CN6134 was originally named C. anaerobium, but for the reasons recently outlined by us (Adlam and Scott) and because it is doubtful whether C. anaerobium should be listed as a distinct species (Johnson and Cummins, 1972), it will be referred to here as C. parvum.The strain of Bord. pertrrssis used (Wellcome Number CN2992) was from a single routine formalised batch of vaccine provided by Mr H. K. Favelle of these laboratories. Organisms were suspended in physiological saline containing 0.01 per cent. thiomersalate as preservative.

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Inheritance of Responsiveness to Pertussis HSF in Mice

Cited by 36 publications

References 14 publications

Analysis of the Role ofBphs/Hrh1in the Genetic Control of Responsiveness to Pertussis Toxin

Analysis of the Role ofBphs/Hrh1in the Genetic Control of Responsiveness to Pertussis Toxin

G Proteins Gα_i1/3Are Critical Targets for Bordetella pertussis Toxin-Induced Vasoactive Amine Sensitization

Studies on the Histamine Sensitisation Produced in Mice by Corynebacterium Parvum

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Inheritance of Responsiveness to Pertussis HSF in Mice

Cited by 36 publications

References 14 publications

Analysis of the Role ofBphs/Hrh1in the Genetic Control of Responsiveness to Pertussis Toxin

Analysis of the Role ofBphs/Hrh1in the Genetic Control of Responsiveness to Pertussis Toxin

G Proteins Gαi1/3Are Critical Targets for Bordetella pertussis Toxin-Induced Vasoactive Amine Sensitization

Studies on the Histamine Sensitisation Produced in Mice by Corynebacterium Parvum

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G Proteins Gα_i1/3Are Critical Targets for Bordetella pertussis Toxin-Induced Vasoactive Amine Sensitization