Platelet activating factor receptors drive CXC chemokine production, neutrophil influx and edema formation in the lungs of mice injected with Tityus serrulatus venom

Coelho, Fernanda; Pessini, Andréa C.; Coelho, Amanda M.; Pinho, Vanessa; Souza, Danielle G.; Arantes, Eliane Candiani; Teixeira, Mauro Martins; Teixeira, Antônio Lúcio

doi:10.1016/j.toxicon.2007.04.009

Cited by 34 publications

(21 citation statements)

References 29 publications

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“…The finding of reduced KC levels in the presence of a higher bacterial burden can at least in part be explained by a diminished capacity of PAFR Ϫ/Ϫ alveolar macrophages to release this chemokine upon stimulation with Pseudomonas LPS. Earlier, it was described that the administration of a PAFR antagonist inhibited the increase of KC lung levels in mice injected with a venom (43), which is in line with our study. The observation that the neutrophil influx and vascular permeability in the venom model were also decreased in the mice in which PAFR was blocked, while these (and other) parameters were increased in our Pseudomonas model, could be due to higher bacterial load in our model.…”

Section: Discussionsupporting

confidence: 93%

Platelet-Activating Factor Receptor Contributes to Host Defense against Pseudomonas aeruginosa Pneumonia but Is Not Essential for the Accompanying Inflammatory and Procoagulant Response

Zoelen

Florquin²,

Meijers

et al. 2008

The Journal of Immunology

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Pseudomonas aeruginosa is a major cause of nosocomial pneumonia, which is associated with high morbidity and mortality. Because of its ubiquitous nature and its ability to develop resistance to antibiotics, it is a problematic pathogen from a treatment perspective. Platelet-activating factor receptor (PAFR) is involved in phagocytosis of several pathogens. To determine the role of PAFR in the innate immune response to P. aeruginosa pneumonia, pafr gene-deficient (PAFR−/−) mice and normal wild-type (Wt) mice were intranasally inoculated with P. aeruginosa. PAFR deficiency impaired host defense as reflected by increased bacterial outgrowth and dissemination in mice with a targeted deletion of the PAFR gene. PAFR−/− neutrophils showed a diminished phagocytosing capacity of P. aeruginosa in vitro. Relative to Wt mice, PAFR−/− mice demonstrated increased lung inflammation and injury as reflected by histopathology, relative lung weights and total protein concentrations in bronchoalveolar lavage fluid, which was accompanied by higher levels of proinflammatory cytokines in lung homogenates and plasma. In addition, PAFR deficiency was associated with exaggerated local and systemic activation of coagulation as determined by fibrin staining of lung tissue and pulmonary and plasma concentrations of thrombin-antithrombin complexes and D-dimer. These data suggest that PAFR is an essential component of an effective host response to P. aeruginosa pneumonia, at least partly via its contribution to the phagocytic properties of professional granulocytes. Additionally, our results indicate that PAFR signaling is not essential for the induction of a local and systemic inflammatory and procoagulant response to Pseudomonas pneumonia.

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Section: Discussionsupporting

confidence: 93%

Platelet-Activating Factor Receptor Contributes to Host Defense against Pseudomonas aeruginosa Pneumonia but Is Not Essential for the Accompanying Inflammatory and Procoagulant Response

Zoelen

Florquin²,

Meijers

et al. 2008

The Journal of Immunology

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“…Scorpion envenoming triggers edema and plasma extravasation through a mechanism that implicates renal filtration changes, as expected by the observed urea concentration increase (14)(15)(16)(17). This will inevitably enhance the gestational physiologic edema and thereby contributes to the increased size of maternal organs (18).…”

Section: Discussionmentioning

confidence: 86%

Embryotoxicity following repetitive maternal exposure to scorpion venom

Hmed¹,

Badraoui²,

Serria³

et al. 2012

J. Venom. Anim. Toxins incl. Trop. Dis

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Abstract:Although it is a frequent accident in a few countries, scorpion envenomation during pregnancy remains scarcely studied. In the present study, the effects of repetitive maternal exposure to Buthus occitanus tunetanus venom are investigated and its possible embryotoxic consequences on rats. Primigravid rats received a daily intraperitoneal dose of 1 mL/kg of saline solution or 300 µg/kg of crude scorpion venom, from the 7 th to the 13 th day of gestation. On the 21 st day, the animals were deeply anesthetized using diethylether. Then, blood was collected for chemical parameter analysis. Following euthanasia, morphometric measurements were carried out. The results showed a significant increase in maternal heart and lung absolute weights following venom treatment. However, the mean placental weight per rat was significantly diminished. Furthermore, blood urea concentration was higher in exposed rats (6.97 ± 0.62 mmol/L) than in those receiving saline solution (4.94 ± 0.90 mmol/L). Many organs of venom-treated rat fetuses (brain, liver, kidney and spleen) were smaller than those of controls. On the contrary, fetal lungs were significantly heavier in fetuses exposed to venom (3.2 ± 0.4 g) than in the others (3.0 ± 0.2 g). Subcutaneous blood clots, microphthalmia and total body and tail shortening were also observed in venom-treated fetuses. It is concluded that scorpion envenomation during pregnancy potentially causes intrauterine fetal alterations and growth impairment.

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“…The extent of neutrophil accumulation and activation was measured by assaying myeloperoxidase (MPO) activity in sera, liver, pancreas and brain homogenates as previously described [14]. Samples were mixed with orthodianisidine (0.167 mg/ml) and H 2 O 2 (0.4 m M ) in phosphate buffer.…”

Section: Methodsmentioning

confidence: 99%

Systemic Responses following Brain Injuries and Inflammatory Process Activation Induced by a Neurotoxin of <b><i>Androctonus</i></b> Scorpion Venom

Taibi-Djennah

Matin-Eauclaire²,

Laraba-Djebari³

2015

Neuroimmunomodulation

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Objective: Kaliotoxin 2 (KTX₂), a neurotoxin isolated from Androctonus australis hector scorpion venom, presents a high affinity with the voltage-gated potassium channels. The targets of KTX₂ in the brain and its toxic effects on the cerebral cortex have been extensively studied; however, its deleterious systemic effects on other organ systems have not yet been investigated. Inflammatory response induced by KTX₂ is supported by cytokine release which could provoke multiple organ dysfunction and diverse biological disorders in mammals. The possibility that inflammatory response and brain injuries induced by KTX₂ may lead to functional disturbances, e.g. in the pancreas and the liver, were investigated. The contribution of IL-6 and TNF-α to the modulation of pathophysiological effects induced by KTX₂ was also tested. Methods: NMRI mice were injected by the intracerebroventricular route with a sublethal dose of KTX₂ or saline solution. Inflammatory response and oxidative stress were assessed in sera and tissue homogenates. Biomarkers of pancreatic and hepatic functions and the correlation with tissue damage in the brain, liver and pancreas were also analyzed. Results: The obtained results revealed that KTX₂ injection induced an inflammatory process activation and imbalanced redox status. It also induced severe alterations in cerebral cortex, hepatic and pancreatic tissues associated with a significant increase in pancreatic and hepatic pathological biomarkers. Cytokine antagonists injected 30 min prior to KTX₂ led to a significant reduction of all disturbances induced by KTX₂. Conclusion: In addition to its significant toxicity on the central nervous system, KTX₂ can also affect pancreatic and hepatic functions, probably by an indirect mechanism involving activation of the inflammatory response with release of IL-6 and TNF-α.

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Platelet activating factor receptors drive CXC chemokine production, neutrophil influx and edema formation in the lungs of mice injected with Tityus serrulatus venom

Cited by 34 publications

References 29 publications

Platelet-Activating Factor Receptor Contributes to Host Defense against Pseudomonas aeruginosa Pneumonia but Is Not Essential for the Accompanying Inflammatory and Procoagulant Response

Platelet-Activating Factor Receptor Contributes to Host Defense against Pseudomonas aeruginosa Pneumonia but Is Not Essential for the Accompanying Inflammatory and Procoagulant Response

Embryotoxicity following repetitive maternal exposure to scorpion venom

Systemic Responses following Brain Injuries and Inflammatory Process Activation Induced by a Neurotoxin of <b><i>Androctonus</i></b> Scorpion Venom

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