Existence of Circulating Mitochondria in Human and Animal Peripheral Blood

• Published in: International journal of molecular sciences Vol. 21; no. 6; p. 2122
• Main Authors: Song, Xiang, Hu, Wei, Yu, Haibo, Wang, Honglan, Zhao, Yelu, Korngold, Robert, Zhao, Yong
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 19.03.2020; MDPI
• Subjects: Adenosine triphosphate; Adult; Animals; Apoptosis; ATP; Autoimmune diseases; B7-H1 Antigen - metabolism; Biological research; blood; Blood circulation; Blood plasma; Blood platelets; CD28 antigen; CD3 antigen; CD4 antigen; CD8 antigen; Cell activation; Cell culture; Cell death; Chemokines; Contamination; Cord blood; CXCR4 protein; Cytokines; Cytokines - metabolism; Cytoplasm; Diabetes; Electron microscopy; Fetal Blood - metabolism; Fetal calf serum; Flow cytometry; Functional analysis; Good Manufacturing Practice; Heat inactivation; Homeostasis; Horses; Humans; immune cells; Immunological tolerance; Inflammation; Inflammation Mediators - metabolism; Lymphocytes; Lymphocytes B; Lymphocytes T; Metabolism; Microscopy; Microscopy, Electron, Transmission; Mitochondria; Mitochondria - metabolism; Mitochondria - ultrastructure; PD-L1 protein; Peptides; plasma; Receptors, CXCR4 - metabolism; serum; Serum Albumin, Bovine - metabolism; Stem cells; Plasma; Serum; Mitochondria; Immune cells; Blood
• DOI: 10.3390/ijms21062122
• ISSN: 1422-0067; 1661-6596

Mitochondria are usually located in the cytoplasm of cells where they generate adenosine triphosphate (ATP) to empower cellular functions. However, we found circulating mitochondria in human and animal blood. Electron microscopy confirmed the presence of mitochondria in adult human blood plasma. Flow cytometry analyses demonstrated that circulating mitochondria from the plasma of human cord blood and adult peripheral blood displayed the immune tolerance-associated membrane molecules such as CD270 and PD-L1 (programmed cell death-ligand 1). Similar data were obtained from fetal bovine serum (FBS) and horse serum of different vendors. Mitochondria remained detectable even after 56 °C heat inactivation. A real-time PCR array revealed purified mitochondria from animal sera expressed several genes that contribute to human T- and B-cell activation. Transwell experiments confirmed the migration capability of mitochondria through their expression of the chemokine receptor CXCR4 in responses to its ligand stromal-derived factor-1α (SDF-1α). Functional analysis established that human plasma mitochondria stimulated the proliferation of anti-CD3/CD28 bead-activated PBMC, up-regulated the percentage of activated CD4 T and CD8 T cells, and reduced the production of inflammatory cytokines. These findings suggested that the existence of circulating mitochondria in blood may function as a novel mediator for cell-cell communications and maintenance of homeostasis. Plasma-related products should be cautiously utilized in cell cultures due to the mitochondrial contamination.