title: The role of microfibrillar-associated protein 4 (MFAP4) in the formation and function of splenic compartments during embryonic and adult life.
abstract: Microfibrillar-associated protein 4 (MFAP4) is an extracellular protein belonging to the fibrinogen-related protein superfamily and is recognized as an integrin ligand with suggested functions in pulmonary and vascular tissue homeostasis. MFAP4 expression in the spleen is increased during infections; however, the significance of MFAP4 for the function of the spleen is unknown. Immunohistochemistry, morphometry and real-time RT-PCR were used to analyze wild-type and MFAP4-deficient spleens. In addition, they were compared with splenic tissue, which was newly formed 8 weeks after avascular implantation into adult mice in order to obtain information about the role of MFAP4 in the formation of splenic tissue during ontogeny and adult life. The present study shows that MFAP4 is co-localized with laminin in the B- and T-cell zones of the spleen, in addition to capsular and trabecular expression. MFAP4 is most likely produced by fibroblastic reticulum cells and follicular dendritic cells of the spleen but can also be imported via the blood from other tissues. The development of splenic tissue is not disturbed in MFAP4-deficient mice. However, in splenic tissue regenerating under MFAP4-deficient conditions, the number of FDCs is significantly decreased but is corrected by MFAP4 imported from other tissues. No differences were observed for lymphocyte numbers or splenic structure. The data indicate that MFAP4 promotes FDC development in regenerating splenic tissue and warrant further investigations regarding the MFAP4 dependency of splenic B-cell maturation.
authors.affiliation: Institute of Histology and Embryology, Faculty of Medicine, University of Beograd, 11000, Beograd, Serbia.
authors.forename: Novica M
authors.initials: NM
authors.lastname: Milićević
authors.affiliation: Center for Structural and Cell Biology in Medicine, Institute of Anatomy, University Lübeck, Ratzeburger Allee 160, D-23538, Lübeck, Germany.
authors.forename: Friederike
authors.initials: F
authors.lastname: Schmidt
authors.affiliation: Center for Structural and Cell Biology in Medicine, Institute of Anatomy, University Lübeck, Ratzeburger Allee 160, D-23538, Lübeck, Germany.
authors.forename: Natalia
authors.initials: N
authors.lastname: Kunz
authors.affiliation: Center for Structural and Cell Biology in Medicine, Institute of Anatomy, University Lübeck, Ratzeburger Allee 160, D-23538, Lübeck, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Kalies
authors.affiliation: Institute of Histology and Embryology, Faculty of Medicine, University of Beograd, 11000, Beograd, Serbia.
authors.forename: Živana
authors.initials: Ž
authors.lastname: Milićević
authors.affiliation: Department of Cancer and Inflammation, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Schlosser
authors.affiliation: Department of Cancer and Inflammation, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
authors.forename: Uffe
authors.initials: U
authors.lastname: Holmskov
authors.affiliation: Department of Cancer and Inflammation, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
authors.forename: Grith Lykke
authors.initials: GL
authors.lastname: Sorensen
authors.affiliation: Center for Structural and Cell Biology in Medicine, Institute of Anatomy, University Lübeck, Ratzeburger Allee 160, D-23538, Lübeck, Germany. westermann@anat.uni-luebeck.de.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Westermann
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D004622:Embryo, Mammalian / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D018858:Germinal Center / Q000166:cytology; D006023:Glycoproteins / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D008810:Mice, Inbred C57BL; D012038:Regeneration; D013154:Spleen / Q000196:embryology*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D007797:Laminin; C000600072:MFAP4 protein, mouse
keywords: Development; Mice; Regeneration; Splenic tissue; Transplantation