الفهرس 
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Abstract
SUMMARY
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SUMMARY
Neutrophils are phagocytic cells whose primary function is • the ingestion and destruction of invading microorganisms. They are small differentiated cells that have lost the ability to divide. Neutrophils are involved in the host defense mechanism against pyogenic infections, their function is closely integrated with that of lymphocytes and macrophages. Cells also involved in the response to infection (8molen and Boxer, 1988). Neutrophils in the blood are attracted to sites of infection by chemotactic factors or chemotoxins, which are generated by the interaction of Antibodies with antigens on pathogens. Chromatoxins are naturally occurring or synthetic substances. It produces directed migration of polymorphonuclear leucocytes towards particles or microorganisms (Synderman et al., 1981).
In addition, an extremely complex group of serum proteins, complement, together with antibodies (both are defined as opsonins) may coat the microorganisms in a process known as opsonization. These proteins can enhance the recognition of the microorganism or particle by phagocytes through binding to specific receptors on the phagocytic cell surface (e.g. Fc receptor, C3b receptor). After recognition these foreign particles are engulfed by the phagocyte and internalized within cytoplasmic vacules,
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to which are fused lysosomal granules, forming the phagosome. These fused granules discharge into the phagocytic vacule potent enzymes capable of degrading a wide variety of biologic substances, including bacterial cell membrane, collagen, elastin and mucopolysaccharides
(Weir, 1988).
Upon recognition of a phagocytic or soluble stimulus, both neutrophils and macrophages experience a ”respiratory burst” which is characterized by an increase in oxygen consumption, activation of the hexose monophosphate shunt and generation of reactive oxygen-derived free radicals and their metabolic products. Granule contents and oxygen metabolites may leak from neutrophils into extracellular fluid where they can injure tissues as well as microbes. This side effect of the attack of neutrophils against antigens or phagosomes may be an important cause of tissue injury and in certain locations may be determintal to the
host (Jandl, 1987).
oxidative processes that are microorganisms can act on adjacent important in the pathogenesis
infectious disease processes. In gouts and autoimmune arthritides, there is a connection between neutrophil
It is demonstrated that the same oxidative and non
in killing
important
host tissues and may be of a number of non-
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accumulation and joint destruction (Weissman and Korchak, 1984). Neutrophil infiltrates may be observed in autoimmune vasculitis and some forms of glomeruloneph-ritis. Neutrophils also have been implicated in the pathogenesis of number of respiratory disorders, including the adult respiratory distress syndrome, emphysema and asthma (Branwuld, 1988).
There is a significant correlation between incidence of coronary heart disease and leucocytic count. Moreover, leucocytic count at an initial examination developing of an average of four years later. This correlation suggest a role for neutrophils in atherogenesis and the subsequent development of ischaemic heart disease (Zalokar et al., 1984).
There is now considerable evidence that neutrophils play an important role in acute myocardial infarction. After acute myocardial infarction, myocardial cell death and damage produce an acute inflammatory response, characterized by migration of neutrophils into the area of infarcted muscle. This infiltration into the infarcted area occurs within 24 hours and the response is maximal at 4-5 days. The influx of neutrophils into infarcted myocardium has usually been regarded as a part of the normal repair process, but the quantity of neutrophils often seems excessive and the neutrophils may be
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destroying ischaemic but potentially viable cells. The mechanisms of leucocyte mediated tissue damage is extensively studied. One of these mechanisms is the mechanical obstruction of coronary microvascular circulation. Leucocytes which are large, stiff and viscous cells, naturally adhere to vascular endothelium and are trapped in myocardial capillaries beginning at the time of coronary occlusion and that further delivery and accumulation by collateral flow during myocardial ischaemia results in leucocyte capillary plugging and increased coronary microvascular resistance and decreased collateral blood flow during ischaemia, in addition, this mechanical obstruction prevent blood flow to the ischaemic myocardium during reperfusion, contributing in part to the development of ”no reflow phenomenon” (Engler at al., 1986).
A second mechanism by which neutrophils can induce tissue damage is due to release of proteolytic enzymes from neutrophilic granules during phagocytosis or cell death. Bell et al. (1986) showed that plasma concentration of human neutrophil elastase were significantly higher in patients after acute myocardial infarction than in healthy volunteers and patients with stable heart disease.
A third mechanism is the role of arachidonic acid metabolites. Exposure of neutrophils to different stimuli
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such as chemotactic factors resulted in the production of lipid mediators from arachidonic acid. Cyclooxygenase and lipoxygenase products play a significant role in the regulation of vascular tone and extension of tissue damage during acute myocardial infarction (Mullane and Moncada,
1982).
Finally and the recently well evaluated is the role of oxygen derived free radicals produced by neutrophils. Oxygen derived free radicals such as superoxide anion and hydrogen peroxide have an important role in the bactericidal activity of phagocytes and also in cell and tissue injury of non-phagocytosed cells. Oxygen free radicals may also be responsible for the depression of ventricular function following reperfusion known as ”stunned myocardium”. It also play a role in the pathogenesis of atherosclerosis (Bolli et al., 1988).
In an effort to protect ischaemic myocardium against these hazardous effects of neutrophils and neutrophilic metabolites, several investigators have demonstrated that reduction of neutrophil counts or attenuation of neutrophil function may protect myocardium during ischaemia and reperfusion. Neutrophils depletion during myocardial infarction in dogs resulted in reduction of the extent of ischaemic myocardial injury and reduction of infarct size (Romson at al., 1983). In accordance of this
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observation attenuation of neutrophil function e.g. by the administration of free radical scavengers e.g superoxide dismutase, also resulted in limitation of infarct size
(McCord at al., 1983).
However, while efforts to salvage ischaemic myocardium pharmacologically should be directed towards the prevention of inappropriate destruction of viable myocardium by neutrophils the potential benefit of reducing myocardial injury must be balanced against the possible untoward effects of impaired healing.