Alternative complement pathway and factor B activities in rats with altered blood levels of thyroid hormone

Abstract

Evaluating the activity of the complement system under conditions of altered thyroid hormone levels might help elucidate the role of complement in triggering autoimmune processes. Here, we investigated alternative pathway (AP) activity in male Wistar rats (180 ± 10 g) after altering their thyroid hormone levels by treatment with triiodothyronine (T3), propylthiouracil (PTU) or thyroidectomy. T3 and thyroxine (T4) levels were determined by chemiluminescence assays. Hemolytic assays were performed to evaluate the lytic activity of the AP. Factor B activity was evaluated using factor B-deficient serum. An anti-human factor B antibody was used to measure factor B levels in serum by radial immunodiffusion. T3 measurements in thyroidectomized animals or animals treated with PTU demonstrated a significant reduction in hormone levels compared to control. The results showed a reduction in AP lytic activity in rats treated with increasing amounts of T3 (1, 10, or 50 µg). Factor B activity was also decreased in the sera of hyperthyroid rats treated with 1 to 50 µg T3. Additionally, treating rats with 25 µg T3 significantly increased factor B levels in their sera (P < 0.01). In contrast, increased factor B concentration and activity (32%) were observed in hypothyroid rats. We conclude that alterations in thyroid hormone levels affect the activity of the AP and factor B, which may in turn affect the roles of AP and factor B in antibody production.

Hypothyroidism symptoms in LT4-euthyroid thyroidectomized patients reflect an alteration of the serum proteome

“…In particular, blood coagulation suggests a proin ammatory response by the dysregulation of thrombin, plasminogen and alpha 1 antitrypsin, while complement activation can participate by altered C3, C1q, C1s and CFAH levels that we found. In accordance with our results, Bitencourtet al indicated that there is a connection between the immune system and thyroid hormones, sinceT3 and T4 hormones affect the lytic potency of the complement system 11 . In particular, we found an up-regulation of fragments that could be generated during the classical, alternative or lectin induced activation of the complement and that have important biological functions, including facilitation of phagocytosis, clearance of immunocomplexes, in ammation, immuneresponse, and tissue homeostasis 12,13 .…”

“…Indeed, our process network analysis suggests that dysregulated proteins involved in blood coagulation and complement system such as CFAH, C3, C1s, Thrombin, Plasminogen, Alpha 1-antitrypsin, are responsible of in ammatory processes both by complement activation , kallikrein-kinin system (KKS) and IL-6 signaling. Complement and KKS are reported to be activated during vascular in ammation 14 and their extensive activation on the endothelium promotes thrombosis, leukocyte recruitment, vascular permeability and vascular wall injury 11,14 . Basically, the complement, coagulation and brinolytic system lead to thrombo in ammation which collectively lead to the activation of blood cells such as polymorphonuclear cells, monocytes, platelets and endothelial cells (EC) lining the vessel 15 .…”

Alteration of Serum Proteome in Levo-Thyroxine-Euthyroid Thyroidectomized Patients

“…This suggests that different complement pathways were activated following thyroidectomy and were maintained in patients that experienced reduced FT3. In accordance with our results, Bitencourt et al indicated that there is a connection between the immune system and thyroid hormones, since T3 and T4 hormones affect the lytic potency of the complement system [ 17 ]. In particular, we found an up-regulation of fragments that could be generated during the classical, alternative, or lectin-induced activation of the complement.…”

“…To our purpose, process network analysis suggests that dysregulated proteins involved in blood coagulation and complement systems, such as CFAH, C3, C1s, Plasminogen, Alpha 1 antitrypsin, may be responsible of inflammatory processes by complement activation, kallikrein-kinin system (KKS) activation, and IL-6 signaling. Complement and KKS are reported to be activated during vascular inflammation [ 20 ] and their extensive activation on the endothelium promotes thrombosis, leukocyte recruitment, vascular permeability, and vascular wall injury [ 17 , 20 ]. Basically, the complement, coagulation, and fibrinolytic systems lead to thrombo-inflammation which collectively leads to the activation of blood cells such as polymorphonuclear cells, monocytes, platelets, and endothelial cells lining the vessels [ 21 ].…”

Transcriptomic and proteomic analyses provide insights into the adaptive responses to the combined impact of salinity and alkalinity in Gymnocypris przewalskii

“…The complement system is responsible for various immune effecter functions, including elimination of invading pathogens, promotion of inflammatory responses, and clearance of apoptotic cells and necrotic cell debris in addition to modulation of adaptive immune responses (Nakao et al 2011 ). Previous studies confirmed the activation of the thyroid pathway appeared to be stimulatory for the humoral immunity in anadromous fish (Bitencourt et al 2012 ; Farkas et al 2008 ; Karkhaneh et al 2019 ; Liu and Lv 2008 ; Yilmazer et al 2003 ; Zwollo 2018 ) and complement could be up-regulated by thyroid hormones in human hepatocellular carcinoma cell lines (Lin et al 2003 ). Although the mechanism of the up-regulation of complement protein under saline–alkaline condition is unclear, we speculated that it might be related to thyroid hormone, considering the enriched pathway of thyroid hormone synthesis from the KEGG analysis (ko04918, q-value = 0.0000) (Additional file 1 : Table S5A).…”