Whether the lung is a primary site of platelet (PLT) production is still disputed. To address this question, PLT parameters in blood before and after pulmonary circulation in humans, rats, and rabbits were assessed by automatic hematology analyzers; bone marrow and pulmonary megakaryocytes in humans, mice, rats, and rabbits were evaluated by immunohistochemical staining; and pulmonary megakaryocytes in humans were analyzed by single-cell RNA sequencing. We found that the mean number of PLTs in rats was nearly threefold greater than that in rabbits and humans. The PLT distribution width after pulmonary circulation in humans, rats, and rabbits was consistently less than that before pulmonary circulation. However, except for the PLT population in the left atrium of rats was significantly greater than that in the right ventricle (n=20), the PLT populations between the left and right atria of rats (n=19), rabbits (n=19), and humans (n=24), between the left atrium and right ventricle of rabbits (n=19), and between the inferior vena cava and radial artery of humans (n=93) had no differences. Moreover, megakaryocytes in the lungs of mice, rats, rabbits, and humans were mononuclear, were mainly located perivascularly, and accounted for approximately 3-5 ‰. Their numbers were significantly lower, and their sizes were smaller than those of bone marrow. Conclusively, the lung can produce PLTs, but it is not a primary site of PLT biogenesis. The capability of pulmonary PLT generation differs among species; at least in rats, it is greater than that in rabbits and humans.

• MeSH
• Adult MeSH
• Rabbits MeSH
• Rats MeSH
• Middle Aged MeSH
• Humans MeSH
• Megakaryocytes metabolism   cytology   MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Lung * cytology   physiology   metabolism   MeSH
• Pulmonary Circulation physiology   MeSH
• Rats, Sprague-Dawley MeSH
• Blood Platelets * cytology   physiology   metabolism   MeSH
• Thrombopoiesis * physiology   MeSH
• Animals MeSH
• Check Tag
• Adult MeSH
• Rabbits MeSH
• Rats MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Mitochondria are considered central regulator of the aging process; however, majority of studies dealing with the impact of age on mitochondrial oxygen consumption focused on skeletal muscle concluding (although not uniformly) a general declining trend with advancing age. In addition, gender related differences in mitochondrial respiration have not been satisfactorily described yet. The aim of the present study was to evaluate mitochondrial oxygen consumption in various organs of aging male and female Fischer 344 rats at the ages of 6, 12 and 24 months. Mitochondrial respiration of homogenized (skeletal muscle, left and right heart ventricle, hippocampus, cerebellum, kidney cortex), gently mechanically permeabilized (liver) tissue or intact cells (platelets) was determined using high-resolution respirometry (oxygraphs O2k, Oroboros, Austria). The pattern of age-related changes differed in each tissue: in the skeletal muscle and kidney cortex of both sexes and in female heart, parameters of mitochondrial respiration significantly declined with age. Resting respiration of intact platelets displayed an increasing trend and it did not correlate with skeletal muscle respiratory states. In the heart of male rats and brain tissues of both sexes, respiratory states remained relatively stable over analyzed age categories with few exceptions of lower mitochondrial oxygen consumption at the age of 24 months. In the liver, OXPHOS capacity was higher in females than in males with either no difference between the ages of 6 and 24 months or even significant increase at the age of 24 months in the male rats. In conclusion, the results of our study indicate that the concept of general pattern of age-dependent decline in mitochondrial oxygen consumption across different organs and tissues could be misleading. Also, the statement of higher mitochondrial respiration in females seems to be conflicting, since the gender-related differences may vary with the tissue studied, combination of substrates used and might be better detectable at younger ages than in old animals.

• MeSH
• Anesthesia MeSH
• Cell Respiration MeSH
• Respiration MeSH
• Muscle, Skeletal metabolism   MeSH
• Rats MeSH
• Mitochondria * MeSH
• Oxygen Consumption physiology   MeSH
• Aging MeSH
• Mitochondria, Muscle * metabolism   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

The objective of the present study was to evaluate platelet mitochondrial oxygen consumption using high-resolution respirometry (HRR) and metabolic flux analysis (MFA) and to verify the effect of advanced age on these parameters. HRR was used to analyze permeabilized and intact platelets, MFA to measure oxygen consumption rates (OCR), extracellular acidification rates (ECAR) and ATP production rate in intact fixed platelets. Two groups of healthy volunteers were included in the study: YOUNG (20-42 years, n=44) and older adults (OLD; 70-89 years; n=15). Compared to YOUNG donors, platelets from group OLD participants displayed significantly lower values of oxygen consumption in the Complex II-linked phosphorylating and uncoupled states and the Complex IV activity in HRR protocols for permeabilized cells and significantly lower resting and uncoupled respirations in intact cells when analyzed by both methods. In addition, mitochondrial ATP production rate was also significantly lower in platelets isolated from older adults. Variables measured by both methods from the same bloods correlated significantly, nevertheless those acquired by MFA were higher than those measured using HRR. In conclusion, the study verifies compromised mitochondrial respiration and oxidative ATP production in the platelets of aged persons and documents good compatibility of the two most widely used methods for determining the global performance of the electron-transporting system, i.e. HRR and MFA.

• MeSH
• Adenosine Triphosphate metabolism   MeSH
• Metabolic Flux Analysis methods   MeSH
• Cell Respiration MeSH
• Adult MeSH
• Energy Metabolism * MeSH
• Hydrogen-Ion Concentration MeSH
• Humans MeSH
• Mitochondria metabolism   MeSH
• Young Adult MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Oxygen Consumption MeSH
• Aging blood   metabolism   MeSH
• Blood Platelets metabolism   MeSH
• Age Factors MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH
• Names of Substances
• Adenosine Triphosphate MeSH