Dr. Murai Éva szerk.: Parasitologia Hungarica 22. (Budapest, 1989)
worms would obviously provide very useful information on the underlying mechanism. However, worm physiology is a relatively neglected, and worm pathophysiology Is an apparently non-existing area of research. Very few results related to this critical facet of host-parasite relationship have been published in recent years. Of those, let me draw your attention to the following stimulating results. RUITENBERG and his associates investigated the production by eosinophils and polymorpho nuclear ce l ls of reactive oxygen metabolites using the lumanol amplified chemilumlnescence method (BUYS, WE VER and RUITENBERG 1984; RUITENBERG and BUYS 1986), in order to extend our knowledge of the interaction between inflammatory cells and target cells of the parasite. It was shown that during adherence eosinophils deposited peroxidase-posltive material on the parasite surface, and eosinophils were high producers of reactive oxygen metabolites. Lysosomal peroxidase enzymes (eosinophil peroxidase, EPO and myeloperoxidase, MPO) possess binding sites for two substrates, H2O2 and chloride ions (Cl~), and catalyze the formation of hypochlorite (OCl"). This highly reactive oxidizing product was supposed to react with the amino groups of proteins bound to the cuticle of nematodes bringing about microlesions. In an in vitro assay system which used EPO and MPO as enzymes, H2O2 and CI" as substrates, and T. spiralis newborn larvae as targets, it was found that OC1" kills the larvae within 20 minutes. It was also found that myeloperoxidases obtained from polymorphonuclear cells and macrophages exhibited a more powerful killing effect than did eosinophil peroxidases (BUYS, WEVER and RUITENBERG 1984; RUITENBERG and BUYS 1986). These in vitro studies present an example of the direct nonspecific mechanisms by which inflammatory cells may affect nematode larvae. It is not known as yet if this cytotoxicity mechanism operates also under in vivo conditions, and when adult worms are the targets . ONWULTRI (1984) studied the effect of anaerobjosis on adenosine triphosphate levels in the infective larval stages of N. brasiliensls and Haemonchus contortus . It was demonstrated that in larvae kept in near anoxic in vitro conditions a fall in the level of ATP develops within 10 min reaching maximum decrease within 60 min. The fall in ATP level curtails energy expenditure resulting in inhibition of active processes such as worm motility. We have also observed that in adult Nippostrongyles under in vitro conditions of oxygen deficiency deoxygenation of worm haemoglobin occurs which is accompanied by increasing immobilisation of the worms (unpublished). Disturbance of the oxygen-dependent energy-producing metabolic processes is likely to be involved in the damage of worms due to immunity . The measurement of ATP content of worms offers a readily measured and sensitive indicator of the degree of metabolic crisis, and this possibility needs be explored. Adult Nippostrongyles are obligate aerobs requiring a minimum PO2 of 1.60 kPa to maintain their energy metabolism. This is available close to the normal mucosal surface by diffusion through the intestinal epithelium. Parasite-induced inflammatory changes include mucosal oedema, and oxygen availability may fall below the level of worm requirement depriving the worms of oxygen and/or other factors vital for their normal physiology. The acute metabolic depression of the worms interferes with their locomotion capacity, and partially paralysed worms will be removed by peristalsis. Here is an example of the indirect nonspecific mechanism of worm damaging. More recently the role of host leukocyte-generated free oxygen radicals has also been implicated in worm expulsion as it was shown that the in vitro survival time of adult Nippo- strongylus brasiliensis was dependent on levels of enzymatic protection against free oxygen radicals (SMITH and BRYANT 1986). The elucidation of the induction, kinetics, and mode of action of free radicals in the mechanism of worm rejection is now the subject of an important line of current research.
