The influence of radiographic contrast media on some granulocyte functions.

Abstract

Radiographic CM are used to change the X-ray absorption of tissue. They have been used since the 1930's and today four main types are available. All these CM are derived from one original structure: the 2,4,6 triiodobenzoic acid with the substituents in positions 1,2 and 5 as a carboxylic group or amides. According to the nature of the substituents and the number of aromatic rings, the four different types of CM can be identified. Three of the four types of CM are hyperosmolar, some of the ionic CM contain meglumine and all CM contain calcium disodium EDTA. To fulfil their role in host defence, circulatory PMN must adhere to endothelium of capillaries and venules adjacent to the inflammatory locus, migrate through the vessel wall to the area of inflammation, phagocytose opsonized bacteria, kill ingested organisms and, finally, inactivate their own toxic products to prevent damage to normal tissue. CM should be biologically inert, but many physiological and pathophysiological effects have been described. This review deals with the present knowledge about the influence of CM on PMN. This thesis presents results of the effects of the four main types of CM on PMN exocytosis of elastase and lactoferrin, adherence to nylon fibers, chemotaxis under agarose and phagocytosis of latex particles, as well after in vitro exposure of CM to PMN and after intravascular injection of CM. After in vitro exposure of CM to whole blood, a dose-dependent fall in lactoferrin and elastase concentration was observed, statistically significant for diatrizoate and ioxaglate at high concentrations. I.v. injection of iohexol or ioxaglate resulted in small, although statistical, decreases in lactoferrin concentration in plasma. No differences between the CM groups were seen. PMN adherence to nylon fibers after incubation of CM with whole blood or isolated PMNs was inhibited. The most inhibitive agents were the ionic CM diatrizoate and ioxaglate. The meglumine ion was found to contribute to the inhibitive effect of diatrizoate upon adherence. Following i.v. injection of iohexol or ioxaglate, increased numbers of PMNs, in combination with decreased adherence, were noted with ioxaglate, and the opposite with iohexol. Immediately after arteriography with iohexol and ioxaglate, a small increase of PMN count, in combination with decreased adherence, could be seen. An inhibition of adherence will result in a shift from the marginal to the circulatory pool of PMNs and thus an increase in PMN count. Although statistically significant the changes were minor. A pronounced increase in PMN count was seen 2-5 hours after arteriography in combination with a decrease in adherence. These changes may be due to a release of glucocorticoids from the adrenals in response to the procedure and/or the injection of CM. CMs do not act as chemoattractants. However, when CM are added to the chemoattractant N-fMLP in the under agarose assay, the number of PMNs migrating (density) was lowered, while the distance migrated by the leading front was not affected except for diatrizoate that almost abolished migration. When diatrizoate was added to PMNs, a dose-dependent inhibition was observed. Following i.v. injection of CM, no changes in PMN chemotaxis or changes in the chemoattractive potential of serum could be demonstrated compared to the baseline levels. The ability of PMNs to ingest latex particles after incubation with CM was inhibited in a dose-dependent way. The most inhibitive agents were diatrizoate and ioxaglate. A solution containing the same amount of disodium calcium EDTA as the CM solutions inhibited phagocytosis significantly, although less than the CM solution. Improved phagocytosis was observed in hyperosmolar environments due to NaCl or mannitol at osmolarities higher than 369 mOsm. I.v. injection of ioxaglate or iohexol inhibited the phagocytosis of latex particles by PMNs. The impairment was most pronounced immediately after the injection, and had almost returned to ba