Changes in Expression of Complement Components in the Ovine Spleen during Early Pregnancy

During early gestation in humans, complement regulation is essential for normal fetal growth. It is supposed that a complement pathway participates in maternal splenic immune regulation at the early stage of gestation in ewes. The aim of this study was to analyze the effects of early pregnancy on the expression of complement components in the maternal spleen of ewes. In this study, ovine spleens were sampled on day 16 of nonpregnancy, and days 13, 16 and 25 of gestation. RT-qPCR, Western blot and immunohistochemical analysis were used to detect the changes in expression of complement components in the ovine maternal spleens. Our results reveal that C1q was upregulated during early gestation, C1r, C1s, C2, C3 and C5b increased at day 25 of gestation and C4a and C9 peaked at days 13 and 16 of gestation. In addition, C3 protein was located in the capsule, trabeculae and splenic cords. In conclusion, our results show for the first time that there was modification in the expression of complement components in the ovine spleen at the early stage of gestation, and complement pathways may participate in modulating splenic immune responses at the early stage of gestation.

Immunomodulatory Proteins in Tick Saliva From a Structural Perspective

To feed successfully, ticks must bypass or suppress the host’s defense mechanisms, particularly the immune system. To accomplish this, ticks secrete specialized immunomodulatory proteins into their saliva, just like many other blood-sucking parasites. However, the strategy of ticks is rather unique compared to their counterparts. Ticks’ tendency for gene duplication has led to a diverse arsenal of dozens of closely related proteins from several classes to modulate the immune system’s response. Among these are chemokine-binding proteins, complement pathways inhibitors, ion channels modulators, and numerous poorly characterized proteins whose functions are yet to be uncovered. Studying tick immunomodulatory proteins would not only help to elucidate tick-host relationships but would also provide a rich pool of potential candidates for the development of immunomodulatory intervention drugs and potentially new vaccines. In the present review, we will attempt to summarize novel findings on the salivary immunomodulatory proteins of ticks, focusing on biomolecular targets, structure-activity relationships, and the perspective of their development into therapeutics.

Sinus venous thrombosis as a complication of COVID-19-associated hypercoagulability

Sinus venous thrombosis (SVT) is an increasingly recognised complication of not only SARS-CoV-2 infections, but also of SARS-CoV-2 vaccinations. SVT is attributed to hypercoagulability, a common complication of COVID-19, disregarding the severity of the infection. Hypercoagulability in COVID-19 is explained by direct activation of platelets, enhancing coagulation, by direct infection and indirect activation of endothelial cells by SARS-CoV-2, shifting endothelial cells from an anti-thrombotic to a pro-thrombotic state, by direct activation of complement pathways, promoting thrombin generation, or by immune thrombocytopenia, which also generates a thrombogenic state. Since SVT may occur even in anticoagulated COVID-19 patients and may have an unfavourable outcome, all efforts must be made to prevent this complication or to treat it accurately.

Targeting the Complement Cascade in the Pathophysiology of COVID-19 Disease

Severe coronavirus disease 2019 causes multi-organ dysfunction with significant morbidity and mortality. Mounting evidence implicates maladaptive over-activation of innate immune pathways such as the complement cascade as well as endothelial dysfunction as significant contributors to disease progression. We review the complement pathways, the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on these pathways, and promising therapeutic targets in clinical trials.

Initiators of Classical and Lectin Complement Pathways Are Differently Engaged after Traumatic Brain Injury—Time-Dependent Changes in the Cortex, Striatum, Thalamus and Hippocampus in a Mouse Model

The complement system is involved in promoting secondary injury after traumatic brain injury (TBI), but the roles of the classical and lectin pathways leading to complement activation need to be clarified. To this end, we aimed to determine the ability of the brain to activate the synthesis of classical and lectin pathway initiators in response to TBI and to examine their expression in primary microglial cell cultures. We have modeled TBI in mice by controlled cortical impact (CCI), a clinically relevant experimental model. Using Real-time quantitative polymerase chain reaction (RT-qPCR) we analyzed the expression of initiators of classical the complement component 1q, 1r and 1s (C1q, C1r, and C1s) and lectin (mannose binding lectin A, mannose binding lectin C, collectin 11, ficolin A, and ficolin B) complement pathways and other cellular markers in four brain areas (cortex, striatum, thalamus and hippocampus) of mice exposed to CCI from 24 h and up to 5 weeks. In all murine ipsilateral brain structures assessed, we detected long-lasting, time- and area-dependent significant increases in the mRNA levels of all classical (C1q, C1s, C1r) and some lectin (collectin 11, ficolin A, ficolin B) initiator molecules after TBI. In parallel, we observed significantly enhanced expression of cellular markers for neutrophils (Cd177), T cells (Cd8), astrocytes (glial fibrillary acidic protein—GFAP), microglia/macrophages (allograft inflammatory factor 1—IBA-1), and microglia (transmembrane protein 119—TMEM119); moreover, we detected astrocytes (GFAP) and microglia/macrophages (IBA-1) protein level strong upregulation in all analyzed brain areas. Further, the results obtained in primary microglial cell cultures suggested that these cells may be largely responsible for the biosynthesis of classical pathway initiators. However, microglia are unlikely to be responsible for the production of the lectin pathway initiators. Immunofluorescence analysis confirmed that at the site of brain injury, the C1q is localized in microglia/macrophages and neurons but not in astroglial cells. In sum, the brain strongly reacts to TBI by activating the local synthesis of classical and lectin complement pathway activators. Thus, the brain responds to TBI with a strong, widespread and persistent upregulation of complement components, the targeting of which may provide protection in TBI.

Unilateral orolingual angioedema in a patient with sarcoidosis after intravenous thrombolysis due to acute stroke without improvement after treatment with icatibant

A potential complication after intravenous administration of recombinant tissue plasminogen activators (rtPAs) for thrombolysis in acute ischaemic stroke is orolingual angioedema, with an incidence of 0.4%–7.9%. In the herewith reported case, we discuss potential links between a history of sarcoidosis and the occurrence of orolingual angioedema after rtPA administration. Sarcoidosis is often accompanied by an elevated ACE level. In contrast, low ACE levels appear to play a role in the pathomechanism currently assumed to trigger angioedema, that is, the activation of the bradykinin and complement pathways. Medication with ACE inhibitors is considered a risk factor for angioedema. Based on these considerations, the patient was also treated with icatibant, a bradykinin B2-receptor antagonist, which has been found useful in recent publications on treating orolingual angioedema after intravenous lysis in ischaemic stroke.