Other neutrophil functions

The cytoskeleton also plays an important role in the regulation of the NADPH oxidase ( 5.3.2). This oxidase is activated by the assembly of in- 

Bengtsson, T., Dahlgren, C., Stendahl, 0., Andersson, T. (1991). Actin assembly and regulation of neutrophil function Effects of cytochalasin B and tetracaine on chemo-tactic peptide-induced 02 production and degranulation. J. Leuk. Biol. 49,236-44. 

Bochsler, P. N., Neilsen, N. R., Dean, D. F., Slauson, D. O. (1992). Stimulus-dependent actin polymerisation in bovine neutrophils. Inflammation 16,383-92. 

Crawford, N., Eggleton, P. (1991). Dynamic changes in neutrophil cytoskeleton during priming and subsequent surface stimulated functions. Biochem. Soc. Trans. 19, 1048-55. 

Downey, G. P., Elson, E. L., Schwab, B. I., Erzurum, S. C., Young, S. K., Worthen, G. S. (1991). Biophysical properties and microfilament assembly in neutrophils Modulation by cyclic AMP. J. Cell Biol. 114, 1179-90. 

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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. 

Exposure of neutrophils to heat shock also results in the synthesis of HSPs and a decrease in their ability to generate reactive oxidants. This is not due to cell death, because the response is reversible and other cellular functions are unaffected. For example, after 20 min exposure at 45 °C, the NADPH oxidase is non-functional, but arachidonic acid release is 73% of control values and PGE2 formation is unaffected. Oxidase activity returns to normal levels 150 min later. Several HSPs are synthesised (e.g. hsp70 and hsp85 at 41 °C, hsp48 and hsp60-65 at 43 °C). (The hsp numbers refer to the relative molecular masses of the proteins.)... 

On the other hand, there are a number of human diseases associated with an overactivity of neutrophil function. Many facets of the neutrophil antimicrobial arsenal, such as reactive oxygen metabolites and proteases, can attack host tissues as effectively as they can attack microbial targets. For this reason, activation of neutrophils under physiological conditions is carefully regulated and damage restricted for the following reasons ... 

Myeloperoxidase is an extremely potent, antimicrobial protein that is present in neutrophils at up to 5% of the total cell protein. Its role in the killing of a wide range of bacteria, fungi, viruses, protozoa and mammalian cells (e.g. tumour cells) is well established from in vitro studies. It also plays an important role in the inactivation of toxins and the activation of latent proteases, as well as in other functions described in section 5.4.1. In view of this apparent central role in neutrophil function during host defence, one would think that any deficiencies in this enzyme would have disastrous consequences on the ability of the host to combat infections. Until the early 1980s, this key role for myeloperoxidase in host protection seemed substantiated by the extremely low incidence of reports of patients with deficiencies of this enzyme. Indeed, up to this time, only 15 cases from 12 families had been reported worldwide. Sometimes these patients were asymptomatic but often suffered Candida infections, particularly if their myeloperoxidase deficiency was also associated with diabetes mellitus. 

Lab test abnormalities Peginterferon alfa-2b alone or in combination with ribavirin capsules may cause severe decreases in neutrophil and platelet counts and abnormality of TSH. In 10% of patients treated with peginterferon alfa-2b, ALT levels rose 2- to 5-fold above baseline. The elevations were transient and were not associated with deterioration of other liver functions. 

Volume therapy with etherified starches in trauma patients results in a reduction in circulating adhesion molecules, an effect that is not observed with albumin infusion (51). Continuous infusion of pentoxifylline did not have a beneficial modulating action on circulating adhesion molecules. Adhesion molecules appear to play an important role in tissue damage secondary to the inflammatory process. Besides neutrophil- and endothelium-bound adhesion molecules, soluble forms have been detected in the circulating blood in trauma patients. They seem to be markers of endothelial damage, but they may also have other biological functions. 

Other proposed functions for Hp or the Hp-hemoglobin complex include inhibition of nitric oxide and prostaglandin synthesis, angiogenesis, and control of lymphocyte and neutrophil function. All of these may be relevant to the control of inflammation. 

The biological role of PF-4 in the regulation of neutrophil function is different from that of IL-8 and other CKs. It... 

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