This section is from the book "Research In Physiopathology As Basis Of Guided Chemotherapy With Special Application To Cancer", by Emanuel Revici. Also available from amazon: Research In Physiopathology
The role of the blood as the secondary part of the entity organism has explained many of the peculiarities of its cells. Aside from the phagocytary functions that can be considered as a particular form of capturation, the leucocytes have to be recognized as acting as holocrine monocellular formations whose specific constituents are liberated by cellular lysis. We have seen that in the case of the neutrophilic granulocytes, the hydrolytic enzymes so liberated, strongly resemble the external secretion of the pancreas. Under this aspect, we have investigated the blood eosinophiles with a role similar to the Paneth cells of the duodenum.
The physiology of these leucocytes has to be sought in the acidophilic character of their granules. Morphological analysis of the eosinophile granule shows that it is formed by a content and a membrane, the last clearly seen in preparations in which the granules have lost their content. Like many other membranes, that of the eosinophile granule can be easily identified as being made partially at least by lipids being stained with dyes dissolving in lipids, such as black Sudan or Scharlach. However, it is the content of the granule with its ability to combine with acid dyes that indicates its specific characters. Under certain circumstances, when the blood is maintained in vitro between the slide and cover object for a certain time, the membrane and granule content are seen to separate. Before this occurrence, a lysis of the eosinophile leucocyte itself takes place. This is manifested through the breakdown of the cellular membrane with the lysis of the nucleus. It is in a second step that the eosinophile granule loses its content. Following it, besides the empty granules and lysed eosinophiles, characteristic Charcot Leyden crystals appear. The correlation between these crystals and eosinophiles has been recognized and is generally accepted as occurring in vivo and in vitro.
Ayer (215) has shortened the process of lysis of the eosinophiles in vitro by treating the blood preparations with a detergent, aerosol. By repeating Ayer's experiments, the relationship between the appearance of the Charcot Leyden crystals and the more complex process of lysis of the eosinophiles has become apparent. It could be seen that the crystals would appear at the site where the nuclei of the eosinophiles disappeared through lysis, and where careful observation of the granules reveals the loss of their eosinophilic content. The presence of empty granule membranes stained by the fatty dyes, in addition to the lysed nuclei, would indicate the conditions under which Charcot Leyden crystals appear. The eosinophilic content of the granule and products induced by the nuclear lysis represent the two factors that together result in these crystals.
Concerning the relationship between Charcot Leyden crystals and eosinophiles, it is interesting to note the difference that exists between eosinophilic granules in various animals. Besides the morphological aspect which can be very different, apparently no Charcot Leyden crystals are obtained from species other than humans and certain simians. This indicates that when the biological role of the eosinophiles is considered, we have to seek another common factor in addition to the morphological and chemical ones. It would seem that it is in their basic reactivity, i.e. in their capacity to bind substances of acid character, that the common character of all eosinophile granules has to be sought. This is also true for the duodenal cells.
Following this view, we initially tended to accord more importance to an antacid property than to any other, seemingly agreeing with other data obtained from this study. Among the substances found to be the principal constituents of these eosinophile granules, the alkaline amino acids, of which arginine is the the principal one, assume a very important role. According to the hypothesis we advance, these alkaline amino acids would represent the active factor of these granules and would be liberated by the eosinophiles when they disintegrate. The eosinophiles would intervene in physiology for the specific purpose of furnishing certain alkaline compounds in whose constitution the alkaline amino acids enter. The solubility of the granule content, when liberated, and the Charcot Leyden crystals indicate, according to this view, that the main character of the eosinophile granule is its capacity to furnish alkaline compounds. Under special circumstances, they are able to act against substances with acid properties that result from the lysis of the nuclei, and together to form the Charcot Leyden crystals.
The relationship of the disintegration of the eosinophile to the surface tension lowering agents is also interesting for the further liberation of the content of these granules. Just as for other granulocytes and lymphocytes, lysis is the characteristic fate of these cells and would constitute their most important character. As seen above, it can be related to the role of blood in the organization, i.e. as the secondary part of the organism level.
As for the other leucocytes, an important factor in the holocrinic role of the eosinophiles has been seen in the necessity of a maturation of these granules for their active intervention. When lysis was induced, it was seen to affect only the cells that had reached a certain degree of maturity, not only for the cells themselves but also for the granules. Young cells, recognized by more intense basophily of the cytoplasm, by lack of, or reduced lobulation of the nucleus, and especially by a neutrophilic or even basophilic character of the granules, do not break down. As in the circulating blood, immature elements are seen, the delay observed in inducing eo sinopenia by various agents can be interpreted as corresponding to the time needed for the circulating eosinophiles to reach maturity, as an essential condition for their lysis. This situation was apparent in a particular case, that of eosinopenia induced through administration of the adrenal corticoids. Although this appears to have a direct effect upon the eosinophiles, a definite time, often even 24 hours, is seen essential in order to achieve the disappearance of the eosinophiles from the circulating blood. This delay has been related to the presence of eosinophiles, allegedly "resistant" to the corticoids. In fact, in studying the eosinophiles which persist after the administration of these hormones, we could see that they represent only immature elements, probably prematurely liberated in larger amounts from the bone marrow. The cells from which some will persist even for 24 hours after administration of corticoneoglucogenic hormones, do not show lysis in vitro nor the appearance of Charcot Leyden crystals, and they present the tinctorial characters of immaturity for the cytoplasm and especially for the granules.