Granule maturation, which corresponds to the acidophilic character, seems to be the essential condition for the lytic intervention of these cells. In the physiological role of eosinophiles, an important aspect of maturation was seen in the relationship between the richness of these elements in the circulating blood and the processes in which a manifest local eosino philia is induced, as through injection of parasite larvae or vegetal oils. A direct relationship between local and sanguine eosinophilia was apparent, the value of the former being the function of the latter. The ability of bone marrow to rapidly compensate the transitory eosinopenia following the passage of these cells into the tissues, has further directly connected the local richness in eosinophiles to the bone marrow's capacity to send new cells into the circulation. In all these changes, the prevailing factor has apparently been the degree of maturity of the eosinophile granulae, which seems to require a certain time to reach the desired degree which is the principal condition also for their physiological intervention.

Correlation between the biological intervention of the eosinophiles and the acidophilic character of the granules and their richness in alkaline amino acids has been confirmed in a study of the basophiles of the blood cells with granules having an opposite character. These granules have an acid content, as seen by their tinctorial affinity for alkaline dyes. They were also observed to contain heparine, a polysulfonated mucoid of frank acid character. The biological antagonism between heparine and alkaline proteins is well known. Protamines, the correspondent of histones for fish, are used to correct the excesses of heparin in the body, especially as therapeutic measures. Therefore, the antagonism between eosinophilic and basophilic granulocytes goes beyond their tinctorial characters.

Through the alkaline reactivity of eosinophiles as related to the fundamental separation of intervening constituents according to their positive or negative character, the antacid eosinophiles could be considered to be in the former group, while the basophiles, rich in lytic heparin, are in the latter.

We shall more fully discuss below the nature of the intervention of the eosinophiles after studying the role of a special group of constituents. For the present, it seems that under abnormal circumstances, exaggeration in the amount of eosinophiles would indicate an existing predominance of conditions that correspond to agents of positive character, i.e., with hetero tropic tendency. The more precise antacid character of these cells further indicates the place that has to be reserved for the eosinophiles in the group of heterotropic agents. Under this aspect, the eosinophile would be seen as an agent of anti acid character in the blood and tissues, conceived to act as a holocrinic cellular gland, i.e., through the lysis of the corresponding cell. Therefore, the richness of the blood and tissues in eosinophiles would indicate a predominance of heterotropic tendency, while paucity in eosinophiles or their absence would indicate a homotropic trend.

Curve of blood eosinophiles in a case of breast adenocarcinoma with multiple metastases

Fig. 212. Curve of blood eosinophiles in a case of breast adenocarcinoma with multiple metastases, showing values persistently below the average line of 100.

In order to understand this aspect of the eosinophiles, we tried to follow the changes in their amount in the blood in relation to normal and abnormal physiology. Study of the changes in the number of eosinophiles in the circulating blood under physiological conditions has indicated the existence of the same 24-hour oscillations as seen for many other constituents of the blood. A relationship is apparent between the periods corresponding to higher or lower quantities of circulating eosinophiles and the degree of activity of the individual. This appears to be opposite in humans who show diurnal activity, and mice and rats that show nocturnal activity. By experimentally changing the hours of light and dark for mice and rats, and through it the time of rest and of activity, the rhythm of change was reversed.

Following the concept of the intervention of eosinophiles in biological balance, we further investigated this aspect of the problem in relation to the dualism in abnormal conditions. Just as for other tests, we obtained an average value in a large series of normal human subjects. Utilizing the Dungar technique for a direct count of eosinophiles, the value of 100 cells/1 cmm. was found to be the average value. An impressive direct correlation could be found between the amount of circulating eosinophiles and the two patterns of abnormality. In one group, that corresponding to type A, the number of eosinophiles appeared not only high but with their values fixed above the average value. High values were observed to persist for long periods of time. Figure 213 shows such a case. For the opposite pattern, corresponding to the fundamental type D, these values appeared to be below 100 and very often 0, persisting for a long period of time. (Fig. 212) In these dual patterns, the degree of abnormality could be related to the deviation in the number of these elements from the average value of 100 elements/1 cmm.

Curve of the blood eosinophiles in a case of generalized melanoma showing values persistently above the average line of 100

Fig. 213. Curve of the blood eosinophiles in a case of generalized melanoma showing values persistently above the average line of 100.

The relative facility with which the number of eosinophiles in the blood of an individual can be determined, has made it an important research tool for information regarding the balance between the two fundamental biological tendencies.