- It is intended for research use only
- The total assay time is less than 3.5 hours
- The kit measures annexin A1 in human serum, plasma (EDTA, citrate, heparin), urine and saliva samples
- Assay format is 96 wells
- Standard is recombinant protein based
- Components of the kit are provided ready to use, concentrated or lyophilized
Apoptosis, Atherosclerosis, Autoimmunity, Cardiovascular disease, Diabetology - Other Relevant Products, Immune Response, Infection and Inflammation, Neural tissue markers, Oncology, Renal disease, Neurodegenerative disease
The annexin superfamily is composed of 12 members in humans, characterized by the unique Ca2+-binding-site architecture, which enables them to peripherally attach to negatively charged membrane surfaces.
Annexin A1 (AnxA1), also known as annexin I or lipocortin I, was characterized as a glucocorticoid-regulated anti-inflammatory protein. This 37-kDa protein is comprised of a homologous core region of 310 amino acid residues, representing almost 90% of the structure, attached to a unique N-terminal region. AnxA1 is a Ca2+-regulated phospholipid-binding protein. To mediate membrane binding, Ca2+ ions can induce a conformational change that leads to the exposure of the bioactive N-terminal domain. The different functions of AnxA1 lie within the unique N-terminus.
AnxA1 is expressed in several tissues and involved in different cell processes including cell survival, proliferation, apoptosis, differentiation and migration. AnxA1 can be nuclear, cytoplasmic and/or membrane-associated. Depending on the human tissue/cell line, AnxA1 can be cleaved at different positions by different proteases. The membrane-associated AnxA1 can be proteolytically cleaved to become accessible to its cognate partners, the formyl-peptide receptors (FPRs). The AnxA1/FPR complex has been found to be involved in inflammation, neuroendocrine system regulation, skeletal muscle differentiation and cancer progression. To date, FPRs are the only known receptors of externalized AnxA1. As these receptors can be activated or silenced by a variety of synthetic ligands, they represent an attractive family of pharmacological targets.
ANXA1 in inflammation:
ANXA1 is able to counter-regulate inflammatory events. ANXA1 and its mimetic peptides inhibit neutrophil tissue accumulation by reducing leukocyte infiltration and activating neutrophil apoptosis. Some evidence has suggested the ability of ANXA1 to induce macrophage reprogramming towards a resolving phenotype, resulting in reduced production of proinflammatory cytokines and increased release of immunosuppressive and pro-resolving molecules. Thus, ANXA1 could be a promising tool for the development of new therapeutic strategies for treating inflammatory diseases.
ANXA1 in cancer:
Deregulation of ANXA1 often correlates with cancer, and its role in tumor initiation, proliferation and metastases has been established. ANXA1 could be a tumorigenic mediator between cancer cells and their microenvironment. Efficient inhibitors of ANXA1 could potentiate cell response to chemotherapy. The overexpression of ANXA1 in the cytoplasm of tumor cells has been observed in several cancers. ANXA1 is specifically expressed in tumor vasculature (at least in breast, kidney, liver, lung, brain and prostate cancers) and could be a promising target for human tumor imaging, drug delivery, and internal radiotherapy. In some cancers, ANXA1 is found at the cell surface, where it stimulates FPRs to trigger oncogenic pathways.
ANXA1 in CVD:
In cardiovascular diseases, the protein has been shown to be beneficial in protecting against inflammation in atherosclerosis, myocardial infarction, and stroke. ANXA1-instructed mechanisms are multidisciplinary and affect leukocytes as well as endothelial cells and tissue-resident cells like macrophages and mast cells. ANXA1 and its derived peptide Ac2–26 are important modulators of the leukocyte adhesion cascade and limit leukocyte recruitment. ANXA1 promotes apoptosis of neutrophils and subsequently efferocytosis by macrophages, it polarizes macrophages toward an anti-inflammatory phenotype with the additional effect of enhanced anti-inflammatory cytokine secretion and a suppressed secretion of inflammatory mediators.
Additionally, much research is focused on the translation of ANXA1 to clinical practice as an attractive protein to halt disease progression and restore homeostasis.
ANXA1 in renal disease:
Leukocyte infiltration presents a hallmark feature of immune-mediated acute kidney injury and defective resolution of inflammation may promote progression towards chronic kidney failure. Leukocytes may either aggravate kidney damage or foster renal repair. The glucocorticoid-inducible protein Annexin A1 has been shown to induce resolution of inflammation and to shift macrophage polarization towards the anti-inflammatory and repair-promoting M2 phenotype.
Measurement of urinary ANXA1 protein levels can help in differentiating minimal change disease (MCD) from other types of glomerular disorders. ANXA1 is a universal biomarker that is helpful in the early diagnosis, prognostic prediction, and outcome monitoring of glomerular injury.
ANXA1 in diabetes and insulin resistance:
Patients with T2DM had elevated plasma levels of ANXA1. Thus, elevated levels of ANXA1 may represent a novel biomarker for the development of hepatosteatosis and hrANXA1 or its peptide mimetics may be useful in the treatment of T2DM and/or its complications. In a mouse model, mice fed a high-fat diet develop insulin resistance, while endogenous ANXA1 dampens the development of both the diabetic phenotype and the associated hepatic steatosis and nephropathy (proteinuria). Treatment with hrANXA1 re-establishes normal insulin signaling and attenuates the development of hepatosteatosis and diabetic nephropathy. Annexin A1 also attenuates microvascular complications through the restoration of Akt signaling in a murine model of type 1 diabetes.
ANXA1 in CNS:
In the central nervous system (CNS), ANXA1 exerts a neuroprotective or anti-neuroinflammatory function by several mechanisms. ANXA1 plays a pivotal role in maintaining blood-brain barrier integrity. Patients with multiple sclerosis have decreased expression of ANXA1 in brain parenchymal capillaries. ANXA1 expression is increased both in the brain of patients with Alzheimer's disease and animal models of Alzheimer's disease at early stages of the disease. ANXA1 regulates amyloid-β phagocytosis in microglia by increasing its enzymatic degradation by neprilysin. ANXA1 plays differing roles in these two diseases. ANXA1is also a central player in the anti-Inflammatory and neuroprotective roles of microglia.
ANXA1, its small peptide mimetics and its receptors have been proposed as exciting new therapeutic targets in the management of a wide range of neuroinflammatory diseases, including stroke and neurodegenerative conditions.