关键词: GPCR Schistosoma mansoni angiotensin II endothelin-1 inflammation pulmonary hypertension α1adrenoceptor

Mesh : Autoantibodies / immunology blood Humans Animals Receptors, G-Protein-Coupled / immunology metabolism Rats Male Female Adult Hypertension, Pulmonary / immunology etiology Middle Aged Myocytes, Cardiac / immunology metabolism parasitology Schistosomiasis mansoni / immunology Schistosoma mansoni / immunology Schistosomiasis / immunology

来  源:   DOI:10.3389/fimmu.2024.1404384   PDF(Pubmed)

Abstract:
UNASSIGNED: Schistosomiasis (SM) is a parasitic disease caused by Schistosoma mansoni. SM causes chronic inflammation induced by parasitic eggs, with collagen/fibrosis deposition in the granuloma process in the liver, spleen, central nervous system, kidneys, and lungs. Pulmonary arterial hypertension (PAH) is a clinical manifestation characterized by high pressure in the pulmonary circulation and right ventricular overload. This study investigated the production of functional autoantibodies (fAABs) against the second loop of the G-protein-coupled receptor (GPCR) in the presence of hepatic and PAH forms of human SM.
UNASSIGNED: Uninfected and infected individuals presenting acute and chronic manifestations (e.g., hepatointestinal, hepato-splenic without PAH, and hepato-splenic with PAH) of SM were clinically evaluated and their blood was collected to identify fAABs/GPCRs capable of recognizing endothelin 1, angiotensin II, and a-1 adrenergic receptor. Human serum was analyzed in rat cardiomyocytes cultured in the presence of the receptor antagonists urapidil, losartan, and BQ123.
UNASSIGNED: The fAABs/GPCRs from chronic hepatic and PAH SM individuals, but not from acute SM individuals, recognized the three receptors. In the presence of the antagonists, there was a reduction in beating rate changes in cultured cardiomyocytes. In addition, binding sites on the extracellular domain functionality of fAABs were identified, and IgG1 and/or IgG3 antibodies were found to be related to fAABs.
UNASSIGNED: Our data suggest that fAABs against GPCR play an essential role in vascular activity in chronic SM (hepatic and PAH) and might be involved in the development of hypertensive forms of SM.
摘要:
血吸虫病(SM)是由曼氏血吸虫引起的寄生虫病。SM引起寄生虫卵引起的慢性炎症,胶原/纤维化沉积在肝脏肉芽肿过程中,脾,脾中枢神经系统,肾脏,还有肺.肺动脉高压(PAH)是以肺循环高压和右心室超负荷为特征的临床表现。这项研究调查了在存在肝和PAH形式的人SM的情况下,针对G蛋白偶联受体(GPCR)的第二个环的功能性自身抗体(fAAB)的产生。
呈现急性和慢性表现的未感染和感染个体(例如,肝肠,肝脾无PAH,并对SM的PAH)进行临床评估,并收集其血液以鉴定能够识别内皮素1,血管紧张素II的fAAB/GPCRs,和a-1肾上腺素能受体。在受体拮抗剂乌拉地尔存在下培养的大鼠心肌细胞中分析了人血清,氯沙坦,BQ123
来自慢性肝和PAHSM个体的fAAB/GPCRs,但不是来自急性SM个体,识别三个受体。在拮抗剂的存在下,培养的心肌细胞的搏动率变化减少。此外,鉴定了fAAB的胞外域功能上的结合位点,发现IgG1和/或IgG3抗体与fAAB相关。
我们的数据表明,抗GPCR的fAAB在慢性SM(肝和PAH)的血管活动中起重要作用,并且可能参与SM的高血压形式的发展。
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