Promotion of platelet aggregation by sera from brucellosis patients with antiphosphatidylcholine antibodies

Casao, María Angeles; Díaz, Ramón; Orduña, Antonio; Gamazo, Carlos

doi:10.1099/0022-1317-50-11-965

Cited by 6 publications

(3 citation statements)

References 5 publications

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“…[5][6][7] The main implicated antibodies in our series, ie, the more unusual antibody subtypes directed against surface cytoplasmic-based antigens (ie, antiphosphatidylserine, antiphosphatidylcholine, antiphosphatidylethanolamine, and anti-beta-2 glycoprotein), have been correlated strongly with EC injury mediated through accelerated apoptosis. [5][6][7][49][50][51][52][53][54][55][56][57][58][59] The EC toxicity assays in 4 of our patients showed morphologic evidence of apoptosis. Further corroboration of a direct role for the antibodies in the induction of microvascular injury is the finding by DIF of immunoglobulin deposition mirroring the specific APAB isotype.…”

Section: Discussionmentioning

confidence: 63%

The Role of Microvascular Injury in the Evolution of Idiopathic Pulmonary Fibrosis

et al. 2003

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Interstitial lung disease compatible with idiopathic pulmonary fibrosis (IPF) developed in 19 previously healthy patients. Although interstitial and/or honeycomb parenchymal fibrosis was present in all, there were patchy areas of paucicellular septal capillary injury along with corroborative direct immunofluorescent evidence of a humorally mediated microvascular injury syndrome. Significantly elevated factor VIII levels were seen in 17 of 18 patients tested. Antiphospholipids were present in all 18 patients tested, comprising antibodies of phosphatidylethanolamine, beta-2 glycoprotein, phosphatidylcholine, and/or phosphatidylserine. Anti-Ro and/or anti-ribonucleoprotein (RNP) antibodies were seen in 4 patients. Serologic evidence of infection with cytomegalovirus (CMV) was found in 9 patients and parvovirus B19 (B19) in 9 patients; 1 patient was not tested. Molecular studies revealed B19 DNA in 6 of 6 B19-seropositive patients. In situ hybridization studies revealed CMV RNA in pulmonary cells in patients with serologic evidence of active CMV infection despite the absence of cytopathic changes typical of CMV infection. Antiphospholipid antibodies, antiendothelial cell antibodies, and/or endotheliotropic viral infections related to B19 and CMV may be of pathogenetic importance to the evolution of IPF. This report underscores the potential importance of microvascular injury in the evolution of IPF.

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Section: Discussionmentioning

confidence: 63%

The Role of Microvascular Injury in the Evolution of Idiopathic Pulmonary Fibrosis

et al. 2003

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“…Several studies demonstrated that patients with chronic brucellosis developed an antibody response against Brucella PC that cross-reacted with platelet-activating factor (PAF), a phospholipid-derived second messenger involved in the inflammatory process with an immunosuppressive role (16,21). Interestingly, those authors found that both the Brucella phospholipid fraction and the patient sera were able to promote platelet aggregation (2,3). These findings and the structural similarity between PC and PAF led those authors to hypothesize that Brucella PC could mimic PAF exerting an agonistic effect upon binding to the PAF receptor that could modulate the inflammatory response generated during infection.…”

Section: Discussionmentioning

confidence: 98%

Brucella abortus Synthesizes Phosphatidylcholine from Choline Provided by the Host

et al. 2006

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The Brucella cell envelope is characterized by the presence of phosphatidylcholine (PC), a common phospholipid in eukaryotes that is rare in prokaryotes. Studies on the composition of Brucella abortus 2308 phospholipids revealed that the synthesis of PC depends on the presence of choline in the culture medium, suggesting that the methylation biosynthetic pathway is not functional. Phospholipid composition of pmtA and pcs mutants indicated that in Brucella, PC synthesis occurs exclusively via the phosphatidylcholine synthase pathway. Transformation of Escherichia coli with an expression vector containing the B. abortus pcs homologue was sufficient for PC synthesis upon induction with IPTG (isopropyl-␤-D-thiogalactopyranoside), while no PC formation was detected when bacteria were transformed with a vector containing pmtA. These findings imply that Brucella depends on choline provided by the host cell to form PC. We could not detect any obvious associated phenotype in the PC-deficient strain under vegetative or intracellular growth conditions in macrophages. However, the pcs mutant strain displays a reproducible virulence defect in mice, which suggests that PC is necessary to sustain a chronic infection process.

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“…LPS increases Lp-PLA 2 mRNA expression in several macrophagerich tissues ( 60 ). Moreover, a previous study indicated the presence of anti-PAF antibodies in patients with Brucella ( 61 ). These antibodies may be the result of a specifi c anti-PAF response.…”

Section: Study Limitationsmentioning

confidence: 99%

Persistence of an atherogenic lipid profile after treatment of acute infection with brucella

Apostolou

Gazi

Kostoula

et al. 2009

Journal of Lipid Research

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This article is available online at http://www.jlr.org herpes simplex virus, helicobacter pylori, as well as periodontitis have been studied ( 2-4 ). On the contrary, other studies have disputed the causal role of infectious agents in atherogenesis ( 5-7 ).Current evidence suggests that atherosclerosis develops as a response to infl ammatory stimulus. Therefore, common or uncommon infections could represent a risk factor. Mechanisms that may be implicated in the atherogenesis caused by infectious agents include local increase of proinfl ammatory cells, local effusion of endotoxins, autoimmune reaction, systemic cytokine release, and changes in lipid metabolism ( 8 ).Infection and infl ammation cause similar cytokineinduced changes in lipid and lipoprotein metabolism ( 9 ). These include reductions in serum levels of total cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), apolipoproteins (Apo) AI and B, and lipoprotein (a) [Lp(a)] and increases in triglyceride (TG) and ApoE concentrations ( 9-14 ).Current evidence suggests that the host response to infection and infl ammation increases oxidized lipids in serum and induces LDL oxidation in vivo. Oxidative modifi cation of LDL is an important event in the development of atherosclerosis ( 15 ). In addition, the cholesterol ester transfer protein (CETP) plays a central role in HDL metabolism and the regulation of HDL-C levels in serum. High levels of CETP activity lead to a reduction in HDL-C levels and an atherogenic lipoprotein profi le ( 16 ).Platelet-activating factor (PAF) is a potent pro-infl ammatory phospholipid produced by activated platelets, -C), ApoB, ApoAI, and ApoCIII and higher LDL-C/HDL-C and ApoB/ApoAI ratios; 2 ) higher levels of IL-1b, IL-6, and TNFa; 3 ) similar ApoCII and oxLDL levels and Lp-PLA 2 activity, lower PON1, and higher CETP activity; and 4 ) higher small dense LDL-C concentration. Four months later, increases in TC, HDL-C, LDL-C, ApoB, ApoAI, and ApoCIII levels, ApoB/ApoAI ratio, and PON1 activity were noticed compared with baseline, whereas CETP activity decreased. LDL-C/HDL-C ratio, ApoCII, and oxLDL levels, Lp-PLA 2 activity, and small dense LDL-C concentration were not altered. Brucella infection is associated with an atherogenic lipid profi le that is not fully restored 4 months following treatment. There is increasing evidence that a link exists between infection/infl ammation and atherosclerosis ( 1 ). Infections with chlamydia pneumoniae, cytomegalovirus,

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Promotion of platelet aggregation by sera from brucellosis patients with antiphosphatidylcholine antibodies

Cited by 6 publications

References 5 publications

The Role of Microvascular Injury in the Evolution of Idiopathic Pulmonary Fibrosis

The Role of Microvascular Injury in the Evolution of Idiopathic Pulmonary Fibrosis

Brucella abortus Synthesizes Phosphatidylcholine from Choline Provided by the Host

Persistence of an atherogenic lipid profile after treatment of acute infection with brucella

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