Intranuclear ferritin

595 INTRANUCLEAR

FERRITINl

R. LADDA2 University

of Chicago, School of Medicine,

Chicago, Ill.,

U.S.A.

Received August 14, 1962

LARGEnumbers

of dispersed and aggregated molecules of ferritin are found in the cytoplasm of reticular cells and erythroblasts of spleen and bone marrow of normal and hypertransfused mice. Moderately to severely anemic animals have only small amounts, if any, ferritin in reticular cells and erythroblasts. Ferritin of spleen and bone marrow is a storage form of iron produced from the degradation of phagocytosed red cells and synthesized from the circulating iron of transferrin. Metabolic acitivity as evidenced by the formation and disappearance of observable ferritin molecules has been generally confined to the cytoplasm [l, 2, 3, 51. Richter found ferritin aggregates in hepatic cell nuclei of rats treated over a 6-month period with large doses of saccharated iron oxide. He proposed two mechanisms for this phenomenon. During cell division fragments of cytoplasm may be incorporated into the nucleus and/or ferritin may be synthesized in the nucleus [6]. This note presents an unusual and related observation made during the course of an investigation of the effects of erythropoietinS on the marrow and spleen of hypertransfused mice. The animal had received 5 intraperitoneal injections of 0.5 cc packed red cells over a 5-day period. The hematocrit was 65 per cent at the time the animal was killed on the 6th day. Peripheral reticulocyte count was 0.015 per cent. The animal was not given erythropoietin and served as a hypertransfused control. Material was fixed in Dalton’s fixative [4] pH 7.4, embedded in methacrylate, and sectioned with a glass knife in the Porter-Blum microtome. Sections were placed on carbon-coated formvar grids, “sandwiched” with a second layer of formvar and observed in the RCA EMU3-d. Figs. 1 and 2 show reticular cell cytoplasm with large aggregations of ferritin particles. Dispersed ferritin particles are also noted. The aggregations are surrounded by a membrane. Mitochondria do not contain ferritin. In addition, in Fig. 2 one observes randomly dispersed ferritin particles within the nucleus. The conditions of this observation are as follows: (1) There is an excess quantity of iron secondary to the hypertransfused state with greatly increased erythrophagocytosis, (2) Hematopoiesis is depressed as judged by absence of mitotic figures from smear preparations of spleen and marrow and low reticulocyte count, (3) Intranuclear ferritin has not been found in normal control animals or hypertransfused animals receiving an erythropoietic stimulating substance. A large quantity of complexed iron is therefore present in a relatively non-proliferating marrow and spleen. 1 Observations were made during the tenure of a U.S.P.H.S. predoctoral traineeship in Pathology. Summer, 1961. Dr. Robert Wissler, Chairman of Department. 2 Senior Medical Student. 8 Erythropoietin was prepared from sheep serum by Armour & Co. and purchased on U.S.P.H.S. Grant H-5393-C-i. Experimental

Cell Research 28

Intranuclear

596

Experimental

Cell Research 28

ferritin

Effect of adrenal steroids on lysosomal enzymes

597

The observation emphasizes the complex nuclear: cytoplasmic interrelationship. The presence of the dispersed intranuclear ferritin could result from migration of the particles from the cytoplasm and/or intranuclear synthesis from freely diffusing precursors throughout the cell. This occurs at a time when the macrophage is overwhelmed with phagocytized red cell debris requiring metabolism. Large sources of iron are therefore available. I wish to thank Dr. William Doyle for the use of his electron microscope and Drs. Benjamin Spargo, Robert \\‘. IVissler, and Clifford Gurney for their criticism. REFERENCES 1. EESSIS, RI. and RRETON-GORIUS, .J., Blood 14, 423 (19.59). 2. __ Compt. Rend. Sci. 245, 1271 (1957). 3. ___ Blood 19, 635 (1962). 4. DALTON, 4. J., Anat. Record 121, 2Sl (1955). 5. LADDA, R., Unpublished observations (1960-61). 6. RICHTER, G. \V., J. Biophys. Biochem. Cqtol. 9, 263 (1961).

EFFECT

OF ADRENAL

LYSOSOMAL

CORTICAL

ENZYMIC

STEROID

ACTIVITIES

OF RAT

G. SACHS, C. deDUVE,J B. S. DVORKIN Department

of Biochemistry,

INJECTION

ON

THYMUS

and A. WHITE

Albert Einstein College of Medicine, New York, N.Y., U.S.A.

Yeshiva

University,

Received August 14, 1962

THE lymphocyte is an end cell of action of certain adrenal cortical steroids [5, 141. The morphological alterations in lymphoid structures resulting from elevated concentrations of blood adrenal cortical steroids have been described in detail [6]. These changes include a budding or shedding of lymphocyte cytoplasm, karyhorrexis of 1 Aided by grants from the American Cancer Society (P6SD), the National Science Foundation (18960), and the National Institutes of Health, United States Public Health Service (2G-563(Cl)) and CY-3154(C5)). 2 Visiting Professor of Biochemistry. Present address: Laboratory of Physiological Chemistry, University of Louvain, Louvain, Relgium, and The Rockefeller Institute, New York, N.Y., U.S.A.

l’ig. l.-Portion x 40,000.

of a reticular

cell showing

dispersed

and aggregations

of ferritin

particles.

Fig. 2.-Portion of another reticular cell. Note the large aggregations of ferritin representing digested fragments of red blood cells. The nucleus contains randomly dispersed ferritin particles. x 40,000. Insert: Various aspects of the dispersed ferritin particles. x 325,000. Experimental

Cell Research 28