Neutrophil functions

Lastly, we will describe how these methods have been used to characterize the effects of hexachlorocyclohexanes on neutrophil functions. Although we are limiting this to a discussion of neutrophils, these approaches are completely generalizable to other cell types and have already been applied to some. We hope this summary will be useful to workers who wish to extend these techniques to the cell systems of interest to them. 

Verspaget, H.W., Pena, A.S., Weterman, I.T. and Earners, C.B.H.W. (1988). Diminished neutrophil function in Crohn s disease and ulcerative colitis identified by decreased oxidative metabolism and low superoxide dismutase content. Gut 29, 223-228. 

Commensal or environmental fungi that are typically harmless can become invasive mycoses when the host immune defenses are impaired. Host immune suppression and risk for opportunistic mycoses can be broadly classified into three categories (1) quantitative or qualitative deficits in neutrophil function, (2) deficits in cell-mediated immunity, and (3) disruption of mechanical/and or microbiologic barriers. 

Politis I, Bizelis I, Tsiaras A and Baldi A (2004), Effect of vitamin E supplementation on neutrophil function, milk composition and plasmin activity in dairy cows in a commercial herd , Journal of Dairy Research, 71, 273-278. 

Follow-on studies are also recommended as needed. These include determination of potential test article effects on blood or tissue immunophenotypes (by flow cytometry or immunohistochemistry), natural killer cell, macrophage, or neutrophil function, host resistance to infection or tumors, and cell-mediated immunity. The important issue in all of these guidelines is this do not ignore signs of immunotoxicity, and assess these findings when observed. 

Queiroz, M.L.S., Almeida, M., Gallao, M.I. et al. Defective neutrophil function in workers occupationally exposed to lead, Pharmacol. Toxicol. 72, 73, 1993. 

Lymphocyte proliferation NK cell activity Neutrophil function Cytokine production... 

Thus, the role of cytokines in inflammation, immune-cell function and tissue repair is varied and complex. Later sections of this book explore the cytokines generated by neutrophils during inflammatory challenge ( 7.3.4), the regulation of neutrophil function by cytokines ( 7.2.1) and human diseases associated with neutrophil dysfunction in which cytokines may play important roles ( 8.2.5, 8.8). 

The varied roles that neutrophils play during the inflammatory response are summarised in Figure 1.16. Many of these individual aspects of neutrophil function are discussed in detail throughout the rest of this book. In summary, neutrophil function is regulated at several steps ... 

IL-3 also has effects on mature cells. Those reported include the enhancement of the cytotoxicity of macrophages, stimulation of the proliferation of tissue-derived mast cells and (in the presence of endotoxin) the stimulation of the tumouricidal activity of monocytes, possibly via enhanced production of tumour necrosis factor (TNF). However, there are no reported effects of IL-3 on mature neutrophil function. 

G-CSF increases the number of progenitor cells in the bloodstream tenfold. It has been used in the treatment of patients with myelodysplastic syndromes (MDS 8.8) where it can increase neutrophil counts and sometimes improve neutrophil function in these patients. Because some leukaemic cells are able to proliferate rather than differentiate in response to G-CSF, this CSF may potentially induce a leukaemic transformation in these patients however, its combined use with cytotoxic agents such as cytosine arabinoside appears to decrease this possibility. No doubt clinical trials already underway will establish the optimal treatment regimen for G-CSF, so that the beneficial effects of this cytokine for the treatment and management of haematological disorders can be realised. 

GM-CSF and IL-3 have been shown to compete for receptors in some types of cells (e.g. eosinophils and KG-1 cells), indicating some structural homology between GM-CSF and IL-3 receptors, perhaps because they share certain subunits or adapter proteins. GM-CSF occupancy results in phosphorylation of certain proteins, and because the receptor possesses no inherent kinase activity, receptor occupancy must be linked to kinase activity via the generation of second messenger molecules. Pretreatment of cells with pertussis toxin abolishes the effects of GM-CSF, indicating the involvement of G-proteins in signal transduction. Priming of neutrophil functions with GM-CSF involves the activation of phospholipases A2 and D. 

A large number of cytokines generated during an inflammatory response can affect neutrophil function. Some of these cytokines, such as G-CSF and GM-CSF, can affect the rate of biosynthesis of mature neutrophils in the bone marrow they can also affect the function of mature cells by priming certain functions (such as the respiratory burst, degranulation and expression of some plasma membrane receptors). These effects are described in detail in Chapters 2 and 7, respectively the present chapter briefly describes some the properties of cytokines known to affect the function of mature neutrophils. 

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