Pasteurella haemolytica leukotoxin enhances production of leukotriene B4 and 5-hydroxyeicosatetraenoic acid by bovine polymorphonuclear leukocytes

Henricks, Paul A.J.; Binkhorst, G. J.; Drijver, Annet A.; Nijkamp, Frans P.

doi:10.1128/iai.60.8.3238-3243.1992

Cited by 39 publications

(22 citation statements)

References 36 publications

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“…Taken together, the results presented here indicate that the Lkt binds to the L 2 integrins. This ¢nding is also consistent with the previously documented effects of the Lkt at sublytic concentrations on the polymorphonuclear neutrophils, such as the induction of in£ammatory cytokines interleukin-1 and tumor necrosis factor-K [16], and other mediators such as leukotriene LTB4 [17], which are known to be mediated by the L 2 integrins [18]. A recent study has identi¢ed CD11/CD18 on mouse peritoneal macrophages as a cellular receptor for the ¢mbriae of Porphyromonas gingivalis [19].…”

Section: Discussionsupporting

confidence: 88%

The leukotoxin of Pasteurella haemolytica binds to β2 integrins on bovine leukocytes

Ambagala¹

1999

FEMS Microbiology Letters

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The putative receptor proteins of Pasteurella haemolytica leukotoxin were isolated from bovine polymorphonuclear neutrophil lysate by affinity chromatography on a leukotoxin-specific monoclonal antibody column to which the leukotoxin was pre-bound. SDS-PAGE of the purified proteins showed four bands at 180 kDa, 170 kDa, 150 kDa and 95 kDa, in addition to the expected 102-kDa leukotoxin band and a series of bands with molecular masses lower than 102 kDa representing the disintegrated leukotoxin. N-terminal amino acid sequencing of the 170-kDa band showed homology with human and murine CD11b. The purified proteins reacted specifically with monoclonal antibodies specific for CD11a, CD11b, CD11c (the K chains of L 2 integrins), and CD18 (the L chain of L 2 integrins). Pre-incubation of polymorphonuclear neutrophils with a monoclonal antibody specific for CD18 reduced the cytotoxicity of the leukotoxin to the cells. These results indicate that the leukotoxin binds to the L 2 integrins on bovine leukocytes, very likely via CD18. ß

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Section: Discussionsupporting

confidence: 88%

The leukotoxin of Pasteurella haemolytica binds to β2 integrins on bovine leukocytes

Ambagala¹

1999

FEMS Microbiology Letters

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“…This ability to affect cytokine release is shared by all the members of the HlyA toxin family; in vitro, LktA and AaltA reduce the lymphocyte response to various stimuli (195,197), at low concentrations, LktA stimulates the production of IL-1 and TNF by bovine mononuclear phagocytes (287,326) and potentiates the production of histamine and certain eicosanoids in response to chemokines (1). LktA and ApxII activate bovine and porcine neutrophils, respectively (63,121,306). These effects may occur without necrotic cell death, since HlyA and AaltA cause apoptosis of human lymphocytes and LktA causes apoptosis of bovine mononuclear cells and granulocytes (142,197).…”

Section: Subversion Of Signal Transduction and Cytokine Productionmentioning

confidence: 99%

Acylation ofEscherichia coliHemolysin: A Unique Protein Lipidation Mechanism Underlying Toxin Function

Stanley

Koronakis

Hughes

1998

Microbiol Mol Biol Rev

177

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SUMMARY The pore-forming hemolysin (HlyA) of Escherichia coli represents a unique class of bacterial toxins that require a posttranslational modification for activity. The inactive protoxin pro-HlyA is activated intracellularly by amide linkage of fatty acids to two internal lysine residues 126 amino acids apart, directed by the cosynthesized HlyC protein with acyl carrier protein as the fatty acid donor. This action distinguishes HlyC from all bacterial acyltransferases such as the lipid A, lux-specific, and nodulation acyltransferases, and from eukaryotic transferases such as N-myristoyl transferases, prenyltransferases, and thioester palmitoyltransferases. Most lipids directly attached to proteins may be classed as N-terminal amide-linked and internal ester-linked acyl groups and C-terminal ether-linked isoprenoid groups. The acylation of HlyA and related toxins does not equate to these but does appear related to a small number of eukaryotic proteins that include inflammatory cytokines and mitogenic and cholinergic receptors. While the location and structure of lipid moieties on proteins vary, there are common effects on membrane affinity and/or protein-protein interactions. Despite being acylated at two residues, HlyA does not possess a “double-anchor” motif and does not have an electrostatic switch, although its dependence on calcium binding for activity suggests that the calcium-myristoyl switch may have relevance. The acyl chains on HlyA may provide anchorage points onto the surface of the host cell lipid bilayer. These could then enhance protein-protein interactions either between HlyA and components of a host signal transduction pathway to influence cytokine production or between HlyA monomers to bring about oligomerization during pore formation.

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“…Eicosanoids, including leukotriene B R (LTB R ), are considered to be important chemotactic agents responsible for in£ux of neutrophils into infected lungs [2]. Leukotoxin (LKT), an RTX protein exotoxin produced by log-phase P. haemolytica, stimulates the release of LTB R from bovine neutrophils [3,4] and also causes neutrophil membrane perturbation and lysis [5]. Exposure of bovine neutrophils to LKT causes a concentrationdependent increase in intracellular calcium concentration ([Ca P ] i ), which stimulates a luminol-dependent chemiluminescence response [6].…”

Section: Introductionmentioning

confidence: 99%

Role of intracellular calcium in Pasteurella haemolytica leukotoxin-induced bovine neutrophil leukotriene B4 production and plasma membrane damage

Cudd

1999

FEMS Microbiology Letters

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Isolated neutrophils were used to study the intracellular calcium ([Ca P ] i ) dependency of Pasteurella haemolytica leukotoxininduced production of leukotriene B R and plasma membrane damage. Exposure of neutrophils to leukotoxin caused a rapid and concentration-dependent increase in [Ca P ] i , followed by simultaneous plasma membrane damage and production of leukotriene B R . Removal of extracellular Ca P , replacement of Ca P with other divalent cations, or exposure to high concentration of verapamil, an inhibitor of voltage-dependent calcium channels, inhibited leukotoxin-induced increases in [Ca P ] i , leukotriene B R production, and membrane damage, thus indicating that influx of extracellular Ca P is necessary to produce these leukotoxin-induced neutrophil responses. z 1999 Published by Elsevier Science B.V. All rights reserved.

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Pasteurella haemolytica leukotoxin enhances production of leukotriene B4 and 5-hydroxyeicosatetraenoic acid by bovine polymorphonuclear leukocytes

Cited by 39 publications

References 36 publications

The leukotoxin of Pasteurella haemolytica binds to β2 integrins on bovine leukocytes

The leukotoxin of Pasteurella haemolytica binds to β2 integrins on bovine leukocytes

Acylation ofEscherichia coliHemolysin: A Unique Protein Lipidation Mechanism Underlying Toxin Function

Role of intracellular calcium in Pasteurella haemolytica leukotoxin-induced bovine neutrophil leukotriene B4 production and plasma membrane damage

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