title: Soluble DPP4 originates in part from bone marrow cells and not from the kidney.
abstract: Dipeptidyl peptidase 4 (DPP4) is known to inactivate incretins as well as important chemokines and neuropeptides. DPP4 is expressed as a transmembrane protein but also occurs as a soluble enzyme circulating in the blood. However, the origin of the soluble DPP4 (sDPP4) is still unknown. In this study, DPP4 activity was quantified in plasma and extracted from different rat organs. Then, in order to see if the kidney or the bone marrow was the source of sDPP4, kidney or bone marrow transplantation was performed between wildtype (wt) Dark Agouti (DA) and DPP4 deficient congenic rats (n=6-9). Kidney was verified to have the highest DPP4 activity, followed by spleen and lung. In the following three weeks after successful kidney transplantation only transient trace plasma DPP4 activity was detected in DPP4 deficient rats receiving wt kidneys. In addition, DPP4 activity was not diminished in DA wt rats receiving DPP4 deficient kidneys. Both findings indicated that sDPP4 did not originate from the kidney. In contrast, 43±14% (compared to wt) sDPP4 activity was detected in the plasma of DPP4 deficient DA rats that were reconstituted with wt bone marrow cells. Not only leukocyte but also macrophage subpopulations express DPP4 in bone marrow as well as in blood as assessed by flow cytometry. Thus, bone marrow derived cells but not the kidney represent at least one source of sDPP4. And leukocyte or macrophage subpopulations could be potential candidates.
authors.affiliation: Department of Nephrology and Hypertension, University of Erlangen-Nürnberg, Loschgestr. 8, 91054 Erlangen, Germany; Department of Urologic Surgery, Union Hospital, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, PR China. Electronic address: wangzhendi@gmail.com.
authors.forename: Zhendi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Division of Nephropathology, University of Erlangen-Nürnberg, Krankenhausstr. 8-10, 91054 Erlangen, Germany. Electronic address: Christina.Grigo@uk-erlangen.de.
authors.forename: Christina
authors.initials: C
authors.lastname: Grigo
authors.affiliation: Division of Nephropathology, University of Erlangen-Nürnberg, Krankenhausstr. 8-10, 91054 Erlangen, Germany. Electronic address: julia.anna.steinbeck@googlemail.com.
authors.forename: Julia
authors.initials: J
authors.lastname: Steinbeck
authors.affiliation: Department for Experimental Therapy, Friedrich-Alexander Universität Erlangen-Nürnberg, Palmsanlage 5, 91054 Erlangen, Germany. Electronic address: stephan.v.hoersten@uk-erlangen.de.
authors.forename: Stephan
authors.initials: S
authors.lastname: von Hörsten
authors.affiliation: Division of Nephropathology, University of Erlangen-Nürnberg, Krankenhausstr. 8-10, 91054 Erlangen, Germany. Electronic address: Kerstin.Amann@uk-erlangen.de.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Amann
authors.affiliation: Division of Nephropathology, University of Erlangen-Nürnberg, Krankenhausstr. 8-10, 91054 Erlangen, Germany. Electronic address: Christoph.Daniel@uk-erlangen.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Daniel
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000201:enzymology*; D018925:Chemokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000097:blood* / Q000378:metabolism; D054795:Incretins / Q000037:antagonists & inhibitors / Q000378:metabolism; D007668:Kidney / Q000201:enzymology*; D016030:Kidney Transplantation; D007962:Leukocytes / Q000201:enzymology; D008264:Macrophages / Q000201:enzymology; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D012995:Solubility
chemical_list: D018925:Chemokines; D054795:Incretins; D009479:Neuropeptides; D018819:Dipeptidyl Peptidase 4
keywords: Bone marrow; CD26; DPP4 deficient rat; Kidney transplantation; Soluble DPP4