Crosstalk between circulating DPP3 and immune cells in the context of cardio-systemic stress

Area of Science:

• Cardiovascular Biology
• Hematology
• Biochemistry

Background:

• Dipeptidylpeptidase 3 (DPP3) is an intracellular peptidase found in circulation (cDPP3).
• cDPP3 is a biomarker and therapeutic target for circulatory failure.
• The origin and release mechanism of DPP3 are not well understood.

Purpose of the Study:

• To investigate the bone marrow's contribution to circulating DPP3 release.
• To elucidate the source of cDPP3, particularly under stress conditions.

Main Methods:

• Bone marrow transplantation from wild-type (WT) to DPP3-knockout (KO) mice (KO^{BM WT}).
• Assessment of cDPP3 activity in stressed and unstressed KO^{BM WT} and WT mice.
• Evaluation of DPP3's effect on cardiac neutrophil infiltration.
• Analysis of DPP3 presence in extracellular vesicles.

Main Results:

• KO^{BM WT} mice recovered 44% of baseline cDPP3 activity, indicating bone marrow contribution.
• Stressed KO^{BM WT} mice showed cDPP3 increases comparable to stressed WT mice.
• DPP3 injection induced cardiac neutrophil infiltration in WT mice.
• Extracellular vesicles contained minimal DPP3, suggesting soluble release.

Conclusions:

• Bone marrow-derived cells are a major source of cDPP3 release during stress.
• These findings support DPP3 as a key player in stress-induced circulatory changes.
• Provides a basis for optimizing DPP3's role as a biomarker and therapeutic target.