European journal of clinical investigation
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Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a membrane protein that plays an important role in a variety of immune and non-immune functions. Such functions are regulated by its activity as a homophilic ligand but also through its ability to interact as a heterophilic ligand with various host proteins. These include CEACAM5, T cell immunoglobulin-mucin like protein-3 (TIM-3) and, potentially, protein death protein 1 (PD-1). ⋯ In this review, we describe the structural basis for CEACAM1 interactions as a homophilic and heterophilic ligand. We discuss the regulation of its monomeric, dimeric and oligomeric states in cis and trans binding as well as the consequences for eliciting downstream signalling activities. Furthermore, we explore the potential role of avidity in determining CEACAM1's activities.
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Eur. J. Clin. Invest. · Dec 2024
ReviewCarcinoembryonic antigen-related cell adhesion molecule 1 in cancer: Blessing or curse?
The Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1, also CD66a), a transmembrane glycoprotein of the immunoglobulin superfamily, is a pivotal mediator of various physiological and pathological processes, including oncologic disorders. However, its precise role in tumorigenicity is contradictory discussed by several clinical studies. This review aims to elucidate the clinical significance of CEACAM1 in different cancer entities focusing on tumour formation, progression and metastasis as well as on CEACAM1-mediated treatment resistance. Furthermore, we discuss the contribution of CEACAM1 to cancer immunity and modulation of the inflammatory microenvironment and finally provide a comprehensive review of treatment regimens targeting this molecule.
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In addition to the long-known antibacterial actions of neutrophils, neutrophils are recognized to have a variety of other effects and are functionally diverse. Neutrophils can either stimulate or inhibit B cells and T cells, regulate NK development and activity, augment or direct the resolution of inflammation, act as myeloid-derived suppressor cells, modulate tumour growth and metastasis and trigger autoimmune diseases. CEACAMs 1, 3, 6 and 8 are expressed on human neutrophils. ⋯ Understanding the exact role of each individual CEACAM in human neutrophils is complicated by the fact that the neutrophil CEACAMs can interact with multiple ligands. The data demonstrates some of the many roles of CEACAMs in neutrophil function and the extensive role of the neutrophil in human biology beyond its classical role as a short-lived phagocyte.
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Eur. J. Clin. Invest. · Dec 2024
ReviewRegulation of lipid storage and inflammation in the liver by CEACAM1.
This review focuses on a special aspect of hepatic lipid storage and inflammation that occurs during nutritional excess in obesity. Mounting evidence supports that prolonged excess fatty acid (FA) uptake in the liver is strongly associated with hepatic lipid storage and inflammation and that the two processes are closely linked by a homeostatic mechanism. There is also strong evidence that bacterial lipids may enter the gut by a common mechanism with lipid absorption and that there is a set point to determine when their uptake triggers an inflammatory response in the liver. ⋯ We start the discussion by introduction of CD36, a major player in FA and lipopolysaccharide (LPS) uptake in the duodenum, liver and adipose tissue. We will then introduce CEACAM1, a major player in the regulation of hepatic de novo lipogenesis and the inflammatory response in the liver, and its dual association with CD36 in enterocytes and hepatocytes. We conclude that CEACAM1 and CD36 together regulate lipid droplet formation and inflammation in the liver.
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Eur. J. Clin. Invest. · Dec 2024
Body temperature, systemic inflammation and risk of adverse events in patients with acute coronary syndromes.
Inflammatory processes can trigger acute coronary syndromes (ACS) which may increase core body temperature (BT), a widely available low-cost marker of systemic inflammation. Herein, we aimed to delineate baseline characteristics of ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation ACS (NSTE-ACS) patients stratified by initial BT and to assess its predictive utility towards major adverse cardiovascular events (MACE) after the index ACS. ⋯ ClinicalTrials.gov Identifier: NCT01000701.