title: Agrin is required for survival and function of monocytic cells.
abstract: Agrin, an extracellular matrix protein belonging to the heterogeneous family of heparan sulfate proteoglycans (HSPGs), is expressed by cells of the hematopoietic system but its role in leukocyte biology is not yet clear. Here we demonstrate that agrin has a crucial, nonredundant role in myeloid cell development and functions. We have identified lineage-specific alterations that affect maturation, survival and properties of agrin-deficient monocytic cells, and occur at stages later than stem cell precursors. Our data indicate that the cell-autonomous signals delivered by agrin are sensed by macrophages through the α-DC (DG) receptor and lead to the activation of signaling pathways resulting in rearrangements of the actin cytoskeleton during the phagocytic synapse formation and phosphorylation of extracellular signal-regulated kinases (Erk 1/2). Altogether, these data identify agrin as a novel player of innate immunity.
authors.affiliation: Istituto Clinico Humanitas, Istituto Di Ricovero e Cura a Carattere Scientifico, Rozzano, Milan, Italy. cristina.mazzon@humanitasresearch.it
authors.forename: Cristina
authors.initials: C
authors.lastname: Mazzon
authors.forename: Achille
authors.initials: A
authors.lastname: Anselmo
authors.forename: Cristiana
authors.initials: C
authors.lastname: Soldani
authors.forename: Javier
authors.initials: J
authors.lastname: Cibella
authors.forename: Cristina
authors.initials: C
authors.lastname: Ploia
authors.forename: Federica
authors.initials: F
authors.lastname: Moalli
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Burden
authors.forename: Michael L
authors.initials: ML
authors.lastname: Dustin
authors.forename: Adelaida
authors.initials: A
authors.lastname: Sarukhan
authors.forename: Antonella
authors.initials: A
authors.lastname: Viola
mesh_terms: D018171:Agrin / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002470:Cell Survival; D049030:Dystroglycans / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D022423:Myeloid Cells / Q000166:cytology* / Q000378:metabolism; D038042:Myelopoiesis; D010587:Phagocytosis; D010766:Phosphorylation
chemical_list: D018171:Agrin; D049030:Dystroglycans; D048049:Extracellular Signal-Regulated MAP Kinases