When granulocytes are labeled with diisopropylfluorophosphate (DFP32) and then returned to the circulation of the donor, the labeled granulocytes are distributed in a pool of cells which is approximately two times larger than that calculated from the blood volume and the concentration of granulocytes in the circulating venous blood (1, 2).This pool has been referred to as the total blood granulocyte pool (TBGP) and it consists of two subcompartments or pools. These pools have been designated the circulating granulocyte pool (CGP) and the marginal granulocyte pool (MGP). The size of the CGP can be calculated from the blood volume and the absolute granulocyte count. Equilibration between the granulocytes in the CGP and in the "noncirculating" or MGP is sufficiently rapid and complete to allow these two pools to be considered as one kinetically, and the size of the TBGP can be determined by the isotope dilution principle. Since the cells are removed from the TBGP in an exponential fashion with a mean half-time disappearance (Ti) of 6.6 hours, the granulocyte turnover rate (GTR), that is, the number of granulocytes turned over through the blood in a unit of time, can be calculated.The purpose of this paper is to present data on the GTR in normal subjects, as well as additional data on the size of the TBGP, CGP and MGP in normal subjects. The influence of steroids, physical exercise, epinephrine and bacterial endotoxin on these parameters in normal subjects has also been studied.

A B S T R A C T The importance of ceruloplasmin in iron metabolism was studied in swine made hypoceruloplasminemic by copper deprivation. When the plasma ceruloplasmin level fell below 1% of normal, cell-to-plasma iron flow became sufficiently impaired to cause hypoferremia, even though total body iron stores were normal. When ceruloplasmin was administered to such animals, plasma iron increased immediately and continued to rise at a rate proportional to the logarithm of the ceruloplasmin dose. The administration of inorganic copper induced increases in plasma iron only after ceruloplasmin appeared in the circulation. Thus, ceruloplasmin appeared to be essential to the normal movement of iron from cells to plasma.Studies designed to define the mechanism of action of ceruloplasmin were based on the in vitro observation that ceruloplasmin behaves as an enzyme (ferroxidase) that catalyzes oxidation of ferrous iron. Retention of injected ferrous iron in the plasma of ceruloplasmin-deficient swine was significantly less than that of ferric iron, reflecting impaired transferrin iron binding. Rat ceruloplasmin, which has little ferroxidase activity, was much less effective than porcine or human ceruloplasmin in inducing increases in plasma iron. These observations suggest that ceruloplasmin acts by virtue of its ferroxidase activity.Eight patients with Wilson's disease were evaluated in order to investigate iron metabolism in a disorder characterized by reduced ceruloplasmin levels. Evidence of iron deficiency was found in six of these, and in five of the six, plasma ceruloplasmin was less than 5% of normal. In comparison, the two patients without evidence of iron deficiency had ceruloplasmin levels of 11 and 18% of normal. It is suggested that iron deficiency tends to occur in those patients with Wilson's disease who have the severest degrees of hypoceruloplasminemia, possibly because of defective transfer of iron from intestinal mucosal cells to plasma.Portions of this work were reported previously in abstract form (1970. J. Clin. Invest. 49: 55 a.) Dr. Lee is a Markle Scholar in Academic Medicine.

In a previous publication (1) it was noted that when granulocytes were labeled in vitro with radioactive diisopropylfluorophosphate (DFP32 ) and then returned to the circulation of the donor, about half of the labeled cells could not be found in the circulation at the completion of the infusion (T0). Thereafter the remaining labeled cells left the circulation in a random fashion with a mean halftime disappearance (T.) of 6.6 hours.Since cell damage and significant elution of the label could not be demonstrated tinder the conditions of the study, it was suggested that the immediate disappearance of half the infused cells was due to their rapid dilution in a larger pool than that calculated from the blood volume and the venous granulocyte count.The concept that the circulating granulocyte pool (CGP) does not constitute all of the intravascular leukocytes is not new. Vejlenis (2)

Although the anaemia associated with chronic disorders is one of the most frequently encountered forms of anaemia, particularly in hospital patients, it has not received the distinction which it deserves, in part, perhaps, because of the lack of an appropriate name. The term ‘simple chronic anaemia’ is most inappropriate because the pathogenesis of the anaemia involves the delicate control mechanisms of erythropoiesis and these are not simple. The title ‘anaemia of chronic infections’ is much too restrictive, for the anaemia occurs in patients with cancer, lymphoma, rheumatoid arthritis, collagen vascular diseases, fractures, severe tissue injury and many other disorders. ‘Anaemia of chronic disorders’, though a less restrictive title, is unsatisfactory because many other types of anaemia occur in these disorders, such as blood loss, overt haemolytic anaemia of various types, reactions to drugs, myelophthisic anaemia, and the anaemia of renal failure. Furthermore, the name gives no hint as to the diagnostic features or pathogenesis of the anaemia. A more descriptive, but somewhat more cumbersome, title might be ‘sideropenic anaemia with reticuloendothelial siderosis.’

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