Annexin 1: more than an anti-phospholipase protein.
Annexin 1 (ANXA1) is the first characterized member of the annexin family of proteins able to bind (i.e. to annex) to cellular membranes in a calcium-dependent manner. ANXA1 may be induced by glucocorticoids in inflammatory cells and shares with these drugs many anti-inflammatory effects. Originally described as a phospholipase A2 (PLA2)-inhibitory protein, ANXA1 can affect many components of the inflammatory reaction besides the metabolism of arachidonic acid. Recent data have shown that ANXA1 may specifically target cytosolic PLA2 by both direct enzyme inhibition and suppression of cytokine-induced activation of the enzyme. ANXA1 inhibits the expression and/or activity of other inflammatory enzymes like inducible nitric oxide synthase (iNOS) in macrophages and inducible cyclooxygenase (COX-2) in activated microglia. The inhibition of iNOS expression may be caused by the stimulation of IL-10 release induced by ANXA1 in macrophages. Like glucocorticoids, ANXA1 exerts profound inhibitory effects on both neutrophil and monocyte migration in inflammation. Several mechanisms may contribute to the protein effect on cell migration, namely the activation of receptors like the formyl peptide receptor (FPR) and the lipoxin A4 receptor (ALXR), the shedding of L-selectin, the binding to alpha4beta1 integrin and carboxylated N-glycans. Furthermore, again mimicking the action of glucocorticoids, ANXA1 promotes inflammatory cell apoptosis associated with transient rise in intracellular calcium and caspase-3 activation. Finally, ANXA1 has been recently identified as one of the 'eat-me' signals on apoptotic cells to be recognised and ingested by phagocytes. Thus, ANXA1 may contribute to the anti-inflammatory signalling that allows safe post-apoptotic clearance of dead cells.
Parente
Luca
L
Department of Pharmaceutical Sciences, University of Salerno, Via Ponte Don Melillo, 84084 Fisciano, Salerno, Italy. lparente@unisa.it
Solito
Egle
E
D000818:Animals; D017305:Annexin A1 / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003600:Cytosol / Q000201:enzymology; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D017305:Annexin A1; D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D019010:Vascular Cell Adhesion Molecule-1; D016753:Interleukin-10; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D010741:Phospholipases A; D054467:Phospholipases A2