Abstract
The complement component C5a and its receptor C5aR1 are involved in the development of numerous inflammatory diseases. In addition to immune cells, C5aR1 is expressed in neoplastic cells of multiple tumour entities, where C5aR1 is associated with a higher proliferation rate, advanced tumour stage, and poor patient outcomes. The aim of the present study was to obtain a broad expression profile of C5aR1 in human non-neoplastic and neoplastic tissues, especially in tumour entities not investigated in this respect so far. For this purpose, we generated a novel polyclonal rabbit antibody, {5227}, against the carboxy-terminal tail of C5aR1. The antibody was initially characterised in Western blot analyses and immunocytochemistry using transfected human embryonic kidney (HEK) 293 cells. It was then applied to a large series of formalin-fixed, paraffin-embedded non-neoplastic and neoplastic human tissue samples. C5aR1 was strongly expressed by different types of immune cells in the majority of tissue samples investigated. C5aR1 was also present in alveolar macrophages, bronchial, gut, and bile duct epithelia, Kupffer cells, occasionally in hepatocytes, proximal renal tubule cells, placental syncytiotrophoblasts, and distinct stem cell populations of bone marrow. C5aR1 was also highly expressed in the vast majority of the 32 tumour entities investigated, where a hitherto unappreciated high prevalence of the receptor was detected in thyroid carcinomas, small-cell lung cancer, gastrointestinal stromal tumours, and endometrial carcinomas. In addition to confirming published findings, we found noticeable C5aR1 expression in many tumour entities for the first time. Here, it may serve as an interesting target for future therapies.
Highlights
The complement system has important functions in innate immunity
Proteases in the complement system circulate as inactive precursors, which are sequentially activated by specific triggers, such as antigen-antibody complexes, foreign material, pathogens, damaged cells, or antigens, or by spontaneous hydrolysis of the complement component C3
The anti-C5aR1 antibody {5227} was further characterised using immunofluorescent staining of transfected cells
Summary
The complement system has important functions in innate immunity. These functions include opsonisation and phagocytosis, inflammation through recruitment of macrophages and neutrophils to sites of infection, and assembly of the membrane attack complex (MAC). Proteases in the complement system circulate as inactive precursors, which are sequentially activated by specific triggers, such as antigen-antibody complexes, foreign material, pathogens, damaged cells, or antigens, or by spontaneous hydrolysis of the complement component C3. One of the most important components of the complement cascade is C5a, which binds to the receptors C5aR1 (CD88). Activated C5aR1, a membrane-bound G-protein coupled receptor (GPCR), increases migration and adhesion of neutrophils and monocytes to vessel walls, resulting in the recruitment of immune cells to sites of infection or antigen-presenting cells to lymph nodes. The function of C5aR2, which is uncoupled from G proteins, remains controversial. C5aR2 may induce G-protein-independent signalling pathways, promoting anti- or pro-inflammatory actions [6,7,8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
