Lack of adenosine A3 receptors causes defects in mouse peripheral blood parameters

Abstract

The role of the adenosine A 3 receptor in hematopoiesis was studied using adenosine A 3 receptor knockout (A 3 AR KO) mice. Hematological parameters of peripheral blood and femoral bone marrow of irradiated and untreated A 3 AR KO mice and their wild-type (WT) counterparts were investigated. Irradiation of the mice served as a defined hematopoiesis-damaging means enabling us to evaluate contingent differences in the pattern of experimentally induced hematopoietic suppression between the A 3 AR KO mice and WT mice. Defects were observed in the counts and/or functional parameters of blood cells in the A 3 AR KO mice. These defects include statistically significantly lower values of blood neutrophil and monocyte counts, as well as those of mean erythrocyte volume, mean erythrocyte hemoglobin, blood platelet counts, mean platelet volume, and plateletcrit, and can be considered to bear evidence of the lack of a positive role played by the adenosine A 3 receptor in the hematopoietic system. Statistically significantly increased values of the bone marrow parameters studied in A 3 AR KO mice (femoral bone marrow cellularity, granulocyte/macrophage progenitor cells, and erythrocyte progenitor cells) can probably be explained by compensatory mechanisms attempting to offset the disorders in the function of blood elements in these mice. The pattern of the radiation-induced hematopoietic suppression was very similar in A 3 AR KO mice and their WT counterparts.

Hematopoiesis in 5-Fluorouracil-Treated Adenosine A3 Receptor Knock-Out Mice

“…Whether these particular findings reflect also in an aggravation of the parameters like oxygen transport capacity, arterial pO 2 , or platelet aggregation test, an additional experimentation is, however, needed. An also previously described (Hofer et al 2014a) obvious increase in the numbers of the bone marrow hematopoietic progenitor cells, GM-CFC and BFU-E, in the A 3 AR KO mice, explainable as an attempt of the hematopoietic system of these mice to compensate for the peripheral blood cell insufficiency, was observed in this study (see Table 4). In the erythroid compartment, the probable compensatory activity in the A 3 AR KO mice was apparently successful, as follows from their significantly higher blood erythrocyte count and blood hemoglobin level (see Table 2).…”

“…Thus, defects have been described in the populations of the mouse peripheral blood erythrocytes and platelets of the A 3 AR KO mice (Hofer et al 2013a). The succeeding studies comprising also exposition of A 3 AR KO mice to ionizing radiation have revealed that the defects at the level of mature peripheral blood cells are attempted to be compensated from the level of the bone marrow progenitor cells (Hofer et al 2014a).…”

Purinergic control of lysenin’s transport and voltage-gating properties

“…Neurotransmission, secretion, transduction, cell proliferation, motility, and differentiation are typical examples of biological functions modulated by nucleotides or nucleosides acting as extracellular signaling molecules [5][6][7][8][9][10][11]. Burnstock's early hypothesis that ATP, the major intracellular molecule providing the energy required for multiple biochemical and biophysical processes, may actually function as an extracellular non-adrenergic and noncholinergic signaling molecule [12,13] was received with great skepticism [14,15].…”

“…Burnstock's early hypothesis that ATP, the major intracellular molecule providing the energy required for multiple biochemical and biophysical processes, may actually function as an extracellular non-adrenergic and noncholinergic signaling molecule [12,13] was received with great skepticism [14,15]. After several decades of extensive work, the scientific community came to the realization that ATP is widely employed as a signaling molecule in multiple biological processes in both normal and pathophysiological conditions [9,11,[16][17][18][19][20][21][22][23][24]. The rapid progress in understanding and deciphering multiple molecular mechanisms of signaling revealed that ATP is a potent mediator of multiple signaling cascades, which may act through binding to, and nonhydrolytic activation of, P2X ionotropic receptors or G Electronic supplementary material The online version of this article (doi:10.1007/s11302-016-9520-9) contains supplementary material, which is available to authorized users.…”

Adenosine signaling inhibits erythropoiesis and promotes myeloid differentiation

“…It is important to note that A 3 activation via its selective agonist IB-MECA has previously been related to the stimulation of granulopoiesis, 24 , 25 and A 3 knockout mice display a reduction in mature granulocytes and monocytes compared to wild-type mice. 26 …”