Research On The Effects Of Low-density Shockwaves On T Cells And Their Biologic Mechanism

A shock wave is elicited by a transient pressure disturbance. Shock waves are characterized by high positive pressure, a rise time lower than 10 ns and tensile wave. The positive pressure and the short rise time are responsible for the direct shock wave effect and the tensile wave for the cavitation, which is called the indirect effect. The fast pressure transition of shock waves (high pressure, short rise time) cause very high tension at the exposed material surfaces so that the structure of the material cracks. Because of this, extracorporeal-generated shock waves were introduced approximately 20 years ago to disintegrate kidney stones. This treatment methed substantially changed the treatment of urolithiasis. Urology, however, is not the medical field for the potential use of shock waves for problems. Shock waves subsequently have been used in orthopaedics and traumatology to treat various insertional tendinopathies (enthesiopathies) and delayed unions and nonunions of fracture. Extracorporeal shock wave therapy has gained increasing acceptance in Europe for some musculoskeletal problems and has led to the inception of clinical studies in the United States. The subsequent researches on biologic mechanism of shock wave treatment on the orthopaedic disorders were carried on in the world. Haupt and Chvapil studies showed that low-density shock wave treatment (10 shock waves at 14kV) led to significant enhancement of reepithelialization of partial-thickness wounds in piglets. Histologically, the upper dermis in the animals that received the treatment had increased numbers of dilated microvessels and increased macrophages in the perivascular spaces. Also, the newly formed epithelial layer was four to five cells thick, almost twice as thick as in control wounds. Wang et al demonstrated that the low-density shock waves (an optimal dose of 500-impulse shock wave treatment at 0.16mJ/mm2) caused a rapid membrane hyperpolarization in 5 min, activation of Ras in 30min, production of specific osteogenic transcription factor (CBFA1) in 6h, enhancement of osteogenic growth factor (TGF-β1) production in 24 h (differentiation of bone marrow stromal cells toward osteoprogenitor associated with induction of TGF-β1), cell proliferation in 2 days, increase of bone alkaline phosphatase activation and collagen type I mRNA expression in 6 days, and osteocalcin mRNA expression in 12 days. Then why can the low-density shock waves (LDSWs) elicit such biological effects on cells? Mechanical stimulation can cause the rapid release of ATP from intracellular plasma. Once released into the extracellular environment, ATP can regulate cell function in an autocrine/paracrine manner by interacting with P2X and /or P2Y receptors that are expressed on the surface of virtually all mammalian cells. Extracellular ATP and its metablic products, including adenosine, which acts via P1 receptors, exert a strong influence on lymphocyte function: ATP can stimulate the proliferation of mouse thymocytes, and ATP and adenosine can antagonize and/or complement T cell receptor-induces signaling, apoptosis, and thymocyte differentiation. LDSWs presumably cause stress forces on the exposed material surface by the high pressure amplitude and the short rise time. LDSWs can be regarded as a kind of mechanical stimulation. What will happen if T cells were exposed to the LDSWs which are able to damage plasma membrane without impairing other organelles? Whether are the LDSWs able to induce the rapid release of ATP from intracellular plasma? And whether is the rapid release of ATP able to elicit the relevant biological effect on T cells?In addition, mechanical stress activates multiple signaling enzymes, including Mitogen activated protein kinase p38 (p38 MAPK). This kinase is structurally related to the yeast protein HOG-1(the products of Saccharomyces cerevisiae osmosensing gene), which is part of the signaling system that allows yeast cells to regulate gene transcription in response to osmotic stress. In human T cells p38 MAPK signaling is involved in t...