Characterization of thromboxane A2 receptor and TRPV1 mRNA expression in cultured sensory neurons

Thromboxane A2 (TxA2) is an arachidonic acid metabolite that stimulates platelet aggregation and vasoconstriction when released from platelets and other cell types during tissue trauma. More recent research has demonstrated that TxA2 can also stimulate vagal and spinal sensory nerves. The purpose of this study was twofold. One, we compared the expression of the TxA2 receptor (TxA2R) in neurons from two sensory ganglia: the nodose ganglion (NG) containing cell bodies of vagal afferent nerves and the thoracic dorsal root ganglion (DRG) containing cell bodies of spinal afferent nerves. Two, we determined if TxA2R co-localizes with mRNA for the nociceptive marker, TRPV1, which is the receptor for the noxious substance capsaicin. We found a greater percentage of neurons in the NG that are positive for TxA2R expression than in the DRG. We also found that there was no correlation of expression of TxA2R with TRPV1. These data suggest that while TxA2R is expressed in both vagal and spinal neurons, TxA2 may elicit stronger vagal or parasympathetic reflexes in the rabbit when released during tissue trauma depending on the location of release. Our data also indicate that TxA2 is likely to stimulate both nociceptive and non-nociceptive neurons thereby broadening the types of neurons and reflexes that it may excite

Haemoglobin C and S Role in Acquired Immunity against Plasmodium falciparum Malaria

A recently proposed mechanism of protection for haemoglobin C (HbC; β6Glu→Lys) links an abnormal display of PfEMP1, an antigen involved in malaria pathogenesis, on the surface of HbC infected erythrocytes together with the observation of reduced cytoadhesion of parasitized erythrocytes and impaired rosetting in vitro. We investigated the impact of this hypothesis on the development of acquired immunity against Plasmodium falciparum variant surface antigens (VSA) encoding PfEMP1 in HbC in comparison with HbA and HbS carriers of Burkina Faso. We measured: i) total IgG against a single VSA, A4U, and against a panel of VSA from severe malaria cases in human sera from urban and rural areas of Burkina Faso of different haemoglobin genotypes (CC, AC, AS, SC, SS); ii) total IgG against recombinant proteins of P. falciparum asexual sporozoite, blood stage antigens, and parasite schizont extract; iii) total IgG against tetanus toxoid. Results showed that the reported abnormal cell-surface display of PfEMP1 on HbC infected erythrocytes observed in vitro is not associated to lower anti- PfEMP1 response in vivo. Higher immune response against the VSA panel and malaria antigens were observed in all adaptive genotypes containing at least one allelic variant HbC or HbS in the low transmission urban area whereas no differences were detected in the high transmission rural area. In both contexts the response against tetanus toxoid was not influenced by the β-globin genotype. These findings suggest that both HbC and HbS affect the early development of naturally acquired immunity against malaria. The enhanced immune reactivity in both HbC and HbS carriers supports the hypothesis that the protection against malaria of these adaptive genotypes might be at least partially mediated by acquired immunity against malaria

Means levels of total IgG against several blood stage antigens of <i>Plasmodium falciparum</i> (AMA1, EBA-175, MSP-1₁₉, MSP-2, MSP-3) and parasite schizont extract in urban samples of Mossi from Ouagadougou, Burkina Faso according to the different haemoglobin genotypes.

<p>The horizontal lines in each box correspond to the median values, the lower edge of each box is the 25% ile and the upper edge is the 75% ile. The whiskers represent the range of the data beyond these percentiles, excluding outliers represented by dots.</p

Mean Fluorescence Intensity (MFI) of total IgG against <i>Plasmodium falciparum</i> A4 Ultra parasite isolate (A4U) and a panel of Composite Isolates (CI) expressing VSA in urban samples of Mossi from Ouagadougou, Burkina Faso according to the different haemoglobin genotypes.

<p>Mean Fluorescence Intensity (MFI) of total IgG against <i>Plasmodium falciparum</i> A4 Ultra parasite isolate (A4U) and a panel of Composite Isolates (CI) expressing VSA in urban samples of Mossi from Ouagadougou, Burkina Faso according to the different haemoglobin genotypes.</p