title: The non-phagocytic route of collagen uptake: a distinct degradation pathway.
abstract: The degradation of collagens, the most abundant proteins of the extracellular matrix, is involved in numerous physiological and pathological conditions including cancer invasion. An important turnover pathway involves cellular internalization and degradation of large, soluble collagen fragments, generated by initial cleavage of the insoluble collagen fibers. We have previously observed that in primary mouse fibroblasts, this endocytosis of collagen fragments is dependent on the receptor urokinase plasminogen activator receptor-associated protein (uPARAP)/Endo180. Others have identified additional mechanisms of collagen uptake, with different associated receptors, in other cell types. These receptors include β1-integrins, being responsible for collagen phagocytosis, and the mannose receptor. We have now utilized a newly developed monoclonal antibody against uPARAP/Endo180, which down-regulates the receptor protein level on treated cells, to examine the role of uPARAP/Endo180 as a mediator of collagen internalization by a wide range of cultured cell types. With the exception of macrophages, all cells that proved capable of efficient collagen internalization were of mesenchymal origin and all of these utilized uPARAP/Endo180 for their collagen uptake process. Macrophages internalized collagen in a process mediated by the mannose receptor, a protein belonging to the same protein family as uPARAP/Endo180. β1-Integrins were found not to be involved in the endocytosis of soluble collagen, irrespectively of whether this was mediated by uPARAP/Endo180 or the mannose receptor. This further distinguishes these pathways from the phagocytic uptake of particulate collagen.
authors.affiliation: Finsen Laboratory/BRIC, Rigshospitalet, DK-2200 Copenhagen, Denmark.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Madsen
authors.forename: Signe
authors.initials: S
authors.lastname: Ingvarsen
authors.forename: Henrik J
authors.initials: HJ
authors.lastname: Jürgensen
authors.forename: Maria C
authors.initials: MC
authors.lastname: Melander
authors.forename: Lars
authors.initials: L
authors.lastname: Kjøller
authors.forename: Amanda
authors.initials: A
authors.lastname: Moyer
authors.forename: Christian
authors.initials: C
authors.lastname: Honoré
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Madsen
authors.forename: Peter
authors.initials: P
authors.lastname: Garred
authors.forename: Sven
authors.initials: S
authors.lastname: Burgdorf
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Bugge
authors.forename: Niels
authors.initials: N
authors.lastname: Behrendt
authors.forename: Lars H
authors.initials: LH
authors.lastname: Engelholm
mesh_terms: D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology; D018938:Caco-2 Cells; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D010587:Phagocytosis; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D037181:Lectins, C-Type; C404106:MRC2 protein, human; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins; C474081:Mrc2 protein, mouse; D011956:Receptors, Cell Surface; D003094:Collagen