Narrow Results

The main objective of this study is to examine the effect of Qi-training on the immune system, especially neutrophil bactericidal function. Nine healthy male subjects were studied for the effects of one bout of ChunDoSunBup (CDSB) Qi-training on superoxide (O₂^-) production and adhesion capacity of neutrophils at times immediately after (Post I) and 2 hours after the Qi-training (Post II). The Qi-training enhanced the (O₂^-) production, reaction velocity and neutrophil adhesion capacity and there were significant differences at Post I compared to before Qi-training (Pre). In addition, the number of white blood cells (WBC), monocytes and lymphocytes were changed significantly through Qi-training. Therefore, it seems that CDSB Qi-training may increase the resistance of trained individuals against common infection and inflammation.

The effect of three amino acid protoporphyrin IX (PPIX) derivatives evaluated as sensitizers in photodynamic therapy — disodium N,N-dialanyl protoporphyrinate (PP(Ala)₂Na₂), diarginine protoporphyrinate (PPArg₂) and diarginine N,N-dialanyl protoporphyrinate (PP(Ala)₂Arg₂) – non-irradiated and pre-irradiated with UV-A, on respiratory burst of non-stimulated and opsonized zymosan stimulated neutrophils was studied. A potential synergistic effect of diazepam (7-chloro-1-methyl-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one) was also examined. PP(Ala)₂Na₂ showed strong pro-oxidant effect towards non-stimulated neutrophils, while PPArg₂ and PP(Ala)₂Arg₂ revealed no significant effect. In the case of stimulated neutrophils all studied porphyrins showed antioxidant effect, although for PP(Ala)₂Na₂ this effect was significantly weaker than that of PPArg₂ and PP(Ala)₂Arg₂. After pre-irradiation with UV-A (λ = 365 nm, fluence 2.0 J.cm^-2, fluence rate 6.7 mW.cm^-2) the antioxidant activity of all studied sensitizers towards non-stimulated granulocytes did not change significantly when compared to effects of non-irradiated porphyrins, while in the case of stimulated cells, only PPArg₂ caused significant decrease of respiratory burst. Non-irradiated diazepam showed significant antioxidant effect and enhanced antioxidant effect of all studied porphyrins towards stimulated neutrophils, while after UV-A pre-irradiation it revealed no significant antioxidant effect on non-stimulated and stimulated neutrophils, both alone and in combination with porphyrin sensitizers.

The study of nanomedicine research, to date, has been concentrating on developing nanovectors for medical imaging, drug/gene delivery, and cell targeting, particularly in cancer diagnosis and therapeutics. Although quite successful in some areas, critical challenges remain, especially in the clinical settings. Some of the critical issues include delivery inefficiency, targeting non-specificity, and low uptake of theranostic-payloads by the cancerous lesions upon intravenous injection. Therefore, an alternative approach may be possible, via nanotechnology, by simulating some of the immune cells. In this Technical Note, we propose using specifically designed nanoparticles to simulate neutrophils that are capable of effective cancer cells targeting and killing without the complications in drug loading, biomarker conjugation, and assembly of chemical and physical therapeutic means. The simulated artificial cells mimic neutrophils, namely, granulocytes, according to their biological characteristics, for instance, positively-charged cell surfaces and the ability to release perferin upon binding onto the cancer cells leading to cytolysis. This Technical Note is intended to deliver a new concept in artificially-engineered granulocytes for cancer diagnosis and therapeutics.

Neutrophil migration and chemotaxis are fundamentally important biological processes and have direct relevance to various health problems. Microfluidic devices provide useful experimental tools for the quantitative analysis of neutrophil chemotaxis in controlled microenvironments. However, such experiments often require specialized research facilities and lengthy cell preparation from a large amount of blood. In this paper, we report a new, yet simple, all-on-chip method for the magnetic isolation of untouched neutrophils directly from small volumes of blood, followed by chemotaxis testing on the same microfluidic device. Furthermore, we incorporated a cell-docking structure to the microfluidic device for better control of the cells’ initial positions before the chemotaxis test and for improved data analysis. The whole experiment can be performed in less than 25 minutes. We successfully validated this method by testing neutrophil chemotaxis to both purified chemoattractant (i.e. fMLP) and clinical samples (sputum from patients with Chronic Obstructive Pulmonary Disease, COPD). Thus, the “all-on-chip” method can be a useful tool for research and clinical applications that require rapid and accurate chemotaxis testing of untouched neutrophils.

Neutrophilic leukocytes are dynamic, motile cells that provide the first line of defense against many infecting organisms. In doing so, neutrophils undergo many of the cellular functions that are known to result from activation of signal transduction pathways. As an end stage cell, the neutrophil is not encumbered by machinery necessary for cellular replication, and thereby has provided an attractive model to define pathways involved in signaling events leading to Ca²⁺ mobilization, actin cytoskeletal dynamics, adherence and chemotactic migration and release of toxic oxygen molecules. The realization that virtually all of the neutrophil's signaling pathways converge to coordinate, regulate and orchestrate the cell's effects has resulted in a new appreciation of how cellular responses are integrated by fundamental biochemical processes in a manner designed to optimize cellular responses.

Neutrophils play an essential role in the body's innate defense against pathogens and are one of the primary mediators of the inflammatory response. To defend the host, neutrophils utilize a wide range of microbicidal products, such as oxidants, microbicidal peptides, and lytic enzymes. The generation of microbicidal oxidants by neutrophils results from the activation of a multi-protein enzyme complex known as the NADPH oxidase, which is responsible for transferring electrons from NADPH to O₂ resulting in the formation of a superoxide anion (O₂^·−). During NADPH oxidase assembly and activation, cytosolic oxidase proteins translocate to the phagosome or plasma membrane, where they assemble around a central membrane-bound component known as flavocytochrome b. This process is highly regulated, involving hosphorylation, translocation, and multiple conformational changes. In this chapter, key structural and functional features of the neutrophil NADPH oxidase and its protein components are described.

Long chain fatty acids such as arachidonic acid regulate key neutrophil functional responses, either directly as free fatty acids or through the generation of biologically active metabolites such as leukotrienes. The metabolites of arachidonic can either promote or suppress neutrophil responses. Alteration in specific structural elements on long chain fatty acids modifies their biological properties, giving rise to a network of lipid mediators which regulate the inflammatory reaction. These fatty acids activate several intracellular signaling molecules, including protein kinase c, mitogen activated protein kinases, phospholipase A₂ and phosphatidyinositol 3 kinase which are relevant to the stimulation of the cellular inflammatory response.

In addition to their phagocytic and killer functions, neutrophils are also a significant source of cytokines, participating in the inflammatory response during infection. A variety of mechanisms are used by the PMN to produce cytokines: release of granular stores of preformed cytokines, de novo synthesis or enzymatic release of membrane-bound form.

The interaction between neutrophils and viruses is complex, and the clinical significance is not well established. It is known that neutrophils can inhibit or kill viruses by various mechanisms, including production of oxygen intermediates and phagocytosis in the laboratory. Viruses may activate neutrophils by binding to the surface and by the production of cytokines which occurs in upper respiratory tract infections. Neutrophils may be inhibited viruses such as CMV by direct interaction by suppression of the bone marrow. These interactions between neutrophils and viruses will be discussed in this chapter.

Neutrophils are the most abundant cells in the human body. Their ability to take up and destroy microorganisms is well known. The potential role of polymorphonuclear neutrophils (PMN) in antitumor response due to their high cytotoxicity was actively investigated in the recent decades. It turned out that the role of PMN in cancer is very complex and controversial. It appears that these cells contribute both in tumor rejection and tumor promotion. The mechanisms of this dual role are starting to emerge. If we could find ways to manipulate PMN function in cancer, it would open a new exciting opportunity to improve cancer therapy. In this chapter, we will discuss the potential role of PMN in tumor growth and cancer therapy.