Abstract
The incidence of megakaryocytic emperipolesis was studied in the bone marrow of normal and X-irradiated mice. Two groups of mice received total body irradiation with a single dose of 5 Gy and one of the two groups had been treated with a radioprotective drug, ethiofos (WR-2721), before irradiation. Mice from a third group remained unexposed to irradiation and served as controls. The Wright-Giemsa stained bone marrow smears were analyzed every 5 days during a 30-day period, starting 1 day after irradiation. The number of megakaryocytes exhibiting the phenomenon was determined and expressed as an average value for every experimental group. The frequency of megakaryocytic emperipolesis was less than 15% of megakaryocytes from control smears but increased to 34% in mice that had only been irradiated and to 43% when mice were treated with WR-2721 before irradiation. In the last case, i.e., irradiation and treatment with a radioprotective drug, a positive correlation between the macrocytic megakaryocytes and elevated emperipolesis was noted. Under light microscopy, there were no signs of phagocytosis; engulfed cells remained unaltered with their normal structure intact. Granulocytic, erythroid, and lymphoid cells appeared to be the most frequent marrow cells engulfed by mature megakaryocytes. The number of incorporated cells in one megakaryocyte ranged from 1 to 3, though occasionally more than 6 were seen in macrocytic megakaryocytes. Based on our findings and on a review of the associated literature, we believe emperipolesis is an interesting cellular phenomenon related to the fast passage of marrow cells across the marrow-blood barrier, especially through the cytoplasm of megakaryocytes in response to an increased demand for cell delivery. The high demand for cell delivery which occurs after irradiation may cause certain mature bone marrow cells to take a transmegakaryocyte path to enter the circulation of the blood. Irradiation seems to have an immediate effect (observed after 24 h) on emperipolesis, suggesting that a humoral factor is involved in the pathogenesis.
Similar content being viewed by others
References
Aoki M, Tavassoli M (1981) Dynamics of red cell egress from bone marrow after blood letting. Br J Haematol 49:337–347
Bobik R (1993) Influence of X-irradiation and radioprotective drug on the megakaryocyte-platelet system of mice (in Polish). Doctoral dissertation, The Jagiellonian University, Cracow
Beutler E (1984) Red cell metabolism. A manual of biochemical methods, 3rd edn. Grune and Stratton, New York
Breton-Gorius J (1981) On the alleged phagocytosis by megakaryocytes. Br J Haematol 47:653
Burkhardt R, Kleinknecht R, Jager R, Frish B, Mahl G, Bartl R (1984) Megakaryocytic emperipolesis — accidental or diagnostic sign? In: Lennert K, Hubner K (eds) Pathology of the bone marrow. G. Fischer, Stuttgart, pp 200–205
Calvo W, Alabi R, Nothdurft W, Fliedner TM (1994) Cytotoxic immigration of granulocytes into megakaryocytes as a late consequence of irradiation. Radiat Res 138:260–265
Cashell AW, Buss DH (1992) The frequency and significance of megakaryocytic emperipolesis in myeloproliferative and reactive states. Ann Hematol 64:273–276
Chiu T (1983) Megakaryocytes with intracytoplasmic blood cells. Am J Vet Res 45:769–770
Humble JG, Jayne WHW, Pulvertaft RJV (1956) Biological interaction between lymphocytes and other cells. Br J Haematol 2:283–294
Larsen TE (1970) Emperipolesis of granular leukocytes within megakaryocytes in human hemopoietic bone marrow. Am J Clin Pathol 53:485–489
Lee KP (1989) Emperipolesis of hematopoietic cells within megakaryocytes in bone marrow of the rat. Vet Pathol 26:473–478
Levine RF, Fedorko ME (1976) Isolation of intact megakaryocytes from guinea pig femoral marrow. Successful harvest made possible with inhibitors of platelet aggregation; enrichment achieved with a two-step separation technique. J Cell Biol 69:159–172
Migita M, Fukunaga Y, Watanabe A, Maruyama K, Ohta K, Kaneko K, Kaneda M, Kakinuma K, Yamatoto M (1992) Emperipolesis of neutrophils by megakaryocytes and thrombocytopenia observed in a case of Kostmann's syndrome during intravenous administration of high-dose rhg-CSF. Br J Haematol 80:413–415
Parmley RT, Kim TH, Austin RL, Avarado CS, Ragab AH (1982) Emperipolesis of neutrophils by dysmorphic megakaryocytes. Am J Hematol 13:303–311
Pasquale De A, Paterlini P, Quaglino D, Quaglino D (1985) Emperipolesis of granulocytes within megakaryocytes (letter). Br J Haematol 60:384–386
Richters A, Sherwin RP, Richters V (1971) The lymphocyte and human lung cancers. Cancer Res 31:214–222
Rozman C, Vives-Corrons (1981) On the alleged diagnostic significance of megakaryocytic ‘phagocytosis’ (emperipolesis) (letter). Br J Haematol 48:510
Sahebekhtiari HA, Tavassoli M (1976) Marrow cell uptake by megakaryocytes in routine bone marrow smears during blood loss. Scand J Haematol 16:13–17
Shamoto M (1981) Emperipolesis of hematopoietic cells in myelocytic leukemia. Virchows Arch [B] 35:283–290
Signal R, Belliveau RR (1988) Quantitation of megakaryocytes in normal bone marrow. Anal Quant Cytol Histol 10:33–36
Sobolewski S (1980) Phagocytosis by megakaryocytes in malignant disorders (abstract). Br J Haematol 45:173
Tavassoli M (1981) Emperipolesis by megakaryocytes in blood loss. Br J Haematol 49:660
Tavassoli M (1986) Modulation of megakaryocyte emperiolesis by phlebotomy: megakaryocytes as a component of marrow-blood barrier. Blood Cells 12:205–216
Tavassoli M, Aoki M (1989) Localization of megakaryocytes in the bone marrow. Blood Cells 15:3–14
Thiele J, Krech R, Choritz H, Georgii A (1984) Emperipolesis — a peculiar feature of megakaryocytes as evaluated in chronic myeloproliferative disease by morphometry and ultrastructure. Virchows Arch [B] 46:253–263
Thiele J, Schneidwer G, Hoeppner B, Wienhold S, Zankovich R, Fischer R (1988) Histomorphometry of bone marrow biopsies in chronic myeloproliferative disorders with associated thrombocytosis — features of significance for the diagnosis of primary (essential) thrombocythemia. Virchows Arch [A] 413:407–417
Weiss L (1970) Transmural cellular passage in vascular sinuses of rat bone marrow. Blood 36:189–208
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bobik, R., Dabrowski, Z. Emperipolesis of marrow cells within megakaryocytes in the bone marrow of sublethally irradiated mice. Ann Hematol 70, 91–95 (1995). https://doi.org/10.1007/BF01834387
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01834387