Differential expression of annexins I, II and IV in human tissues: an immunohistochemical study

Abstract

Annexins constitute a family of Ca2+- and phospholipid-binding proteins. Although their functions are still not clearly defined, several members of the annexin family have been implicated in membrane-related events along exocytotic and endocytotic pathways. To elucidate a possible correlation of those functional proposals with the tissue distribution of annexins, we analysed immunohistochemically the expression of annexins I, II and IV in a broad variety of human tissues. Annexins I and II were chosen for this study since their functionally relevant N-terminal domains are structurally closely related, whilst annexin IV is structurally less related to the former two proteins. The study revealed distinct expression patterns of annexins I, II and IV throughout the body. Annexin I was found in leucocytes of peripheral blood, tissue macrophages and T-lymphocytes and in certain epithelial cells (respiratory and urinary system, superficial cells of non-keratinised squamous epithelium), annexin II in endothelial cells, myoepithelial cells and certain epithelial cells (mainly respiratory and urinary system), whereas annexin IV was almost exclusively found in epithelial cells. Epithelia of the upper respiratory system, Bowman's capsule, urothelial cells, mesothelial cells, peripheral nerves, the choroid plexus, ependymal cells and pia mater and arachnoid of meninges generally strongly expressed all three annexins investigated. The characteristic expression in different tissues and the intracellular distribution indicates that the three annexins investigated are involved in aspects of differentiation and/or physiological functions specific to these tissues.

An immune response manifested by the common occurrence of annexins I and II autoantibodies and high circulating levels of IL-6 in lung cancer

“…The annexins belong to a family of multifunctional, calciumdependent, phospholipid-binding proteins (18). Prior studies have shown that, in the lung, annexins I and II were expressed in cilia and pleural mesothelial cells but not in Clara cells (19). Annexin I but not annexin II was found to be expressed in epithelium.…”

Annexin II represents metastatic potential in clear-cell renal cell carcinoma

“…The ANX2 heterotetramer acts as a receptor for plasminogen, tissue-type plasminogen activator and tenascin C, and is implicated in extracellular matrix degradation (Gerke et al, 2005). The ANX2 is not observed in normal hepatocytes, the pancreatic exocrine system and the mammary gland (Frohlich et al, 1990;Dreier et al, 1998;MasseyHarroche et al, 1998); in tumours that arise from these tissues, such as hepatocellular carcinoma, pancreatic cancer and breast cancer, respectively, ANX2 expression is observed as membrane and/or cytoplasmic staining (Frohlich et al, 1990;Diaz et al, 2004;Sharma et al, 2006). Esposito et al (Esposito et al, 2006) reported that ANX2 expression changed from cytoplasmic to cell surface expression with progression of pancreatic cancer.…”

Gene Expression Profiling of Alcoholic Liver Disease in the Baboon (Papio hamadryas) and Human Liver

“…In the normal liver, moderate expression of different annexins has been reported in the cytoplasm, bile duct, nuclear membrane, hepatocytes, and Kupffer cells. 45 Annexin A2 was immunolocalized in the bile duct but not in hepatocytes in the normal liver. 45 Immunofluorescence showed a marked increase in the expression of annexin A2 protein in human ALD at the hepatocyte cell surface, proliferating bile ducts, and in other small liver cells (Figure 7).…”

“…45 Annexin A2 was immunolocalized in the bile duct but not in hepatocytes in the normal liver. 45 Immunofluorescence showed a marked increase in the expression of annexin A2 protein in human ALD at the hepatocyte cell surface, proliferating bile ducts, and in other small liver cells (Figure 7). The Veterans Affairs Cooperative study 46 on alcoholic hepatitis reported proliferation of interlobular and marginal bile ducts with metaplasia and cells resembling oval cells in 122 human biopsy samples.…”