Nov 29, 1978 - spleen, bone marrow, thymus and placenta of guinea pigs under endogenous or exogenous ... (FK) cells (Welsh, 1966; Kortelainen and.
Br. J. exp. Path (1979) 60, 276
A LIGHT AND ELECTRON MICROSCOPE STUDY ON THE ORIGIN OF FOA-KURLOFF CELLS C. KITTAS, M. A. PARSONS AND L. HENRY From the Department of Pathology, University of Sheffield Medical School, Beech Hill Road, Sheffield S1O 2RX, England Received for publication November 29, 1978
Summary.-Numerous Foa-Kurloff (FK) cells have been found in the circulation, spleen, bone marrow, thymus and placenta of guinea pigs under endogenous or exogenous oestrogenic stimulation. The origin of these cells is obscure. In the present experiment, the distribution of FK cells in organs other than those stated above was studied following gonadectomy and hexoestrol administration in guinea pigs of both sexes for either 1 or 10 weeks. More FK cells than those expected from the vascularity of the organ were found in the liver and lungs of male and female animals. The number of FK cells in these organs was larger after the long-term treatment with hexoestrol and it was accompanied by a significant decrease in the number of Kupffer cells of the liver. The latter observation is in contrast to previous reports of increased numbers of Kupffer cells in the liver of oestrogen-receiving mice, a species not producing FK cells. These observations suggest a relation between the two types of cells. No transformation of mature Kupffer cells into FK cells was seen with the electron microscope. However, other findings suggest that both Kupifer cells and FK cells may well be derived from a common precursor of MPS in the bone marrow.
IN 1889 Kurloff and, independently, Foa and Carbonne described a unique inclusion body in the cytoplasm of mononuclear cells in the guinea pig. Ledingham (1940) demonstrated that the formation of this inclusion body was strictly related to oestrogenic stimulation. Since then, many different views have been expressed concerning the nature of this inclusion and differing conclusions were drawn about the origin of the affected cells. The inclusion body has been described as containing material comparable to that found in cells in cases of storage disease (Mittwoch, 1961) or phagocytosed erythrocytes (Barer, Bradbury and Meek, 1963) but it is now accepted that it is actively synthesized by the so-called Foa-Kurloff (FK) cells (Welsh, 1966; Kortelainen and Korhonen, 1976b). It has been demonstrated that the inclusion body is composed of a mucoproteinsulphated mucopolysaccharide complex
(Marshall and Swettenham, 1959). Muir and Marshall (1961) originally considered that the sulphated mucopolysaccharide was similar to chondroitin sulphate but later Dean and Muir (1970) showed that there were several differences between these two substances. Phospholipids were also identified at the periphery of the inclusion. (Kortelainen and Korhonen, 1976a).
The FK cells have been considered as lymphocytes (Bimes et al., 1964; Welsh, 1966) and as macrophages (Barer and Joseph, 1965). Revell, Vernon-Roberts and Gray (1971) and Kortelainen and Korhonen (1976b) concluded that the FK cells cannot be classified as belonging to any particular cell type, although they certainly belong to the lymphoreticular system. The main organs of production of these cells may be the thymus (Bimes et al., 1964; Simmons, 1965) or the spleen (Sandberg, 1970; Ernstrom and Sandberg, 1971)
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but FK cells are not found in lymph nodes. However, it has been shown that the rate of formation of FK cells is not influenced by thymectomy (Ranlov, Christensen and Wanstrup, 1970) and is even increased by splenectomy (Heinle and Heydinger, 1944). These observations led to the suggestion that other organs may well be involved in the production of FK cells; bone marrow was considered as such a possible source by Kortelainen and Korhonen (1 976b). A few papers report the presence of these cells in other organs, always located in vascular spaces (Revell et al., 1971; Kortelainen and Korhonen, 1976b), large numbers occurring in the lungs and the liver of oestrogen-receiving guinea pigs. These organs are known to contain two members of the mononuclear phagocyte system (MPS), the alveolar macrophage and the Kupffer cell. Since the effect of oestrogens on the MPS has been well established (Nicol et al., 1964; Vernon-Roberts, 1969) an experiment was performed to study the distribution of FK cells in guinea pigs with emphasis on the liver and lung. A possible relation between FK cells and members of the MPS was also investigated. MATERIALS AND METHODS
Sixteen male and 16 female guinea-pigs were
uised (average body wt 400 and 350 g respec-
tively). Four animals of each sex were subjected to gonadectomy and in 8 more gonadectomy was subsequently followed by implantation of a pellet containing hexoestrol. Four male and 4 female guinea-pigs were used as controls. Orchidectomy was performed under ether anaesthesia, through a small transverse suprapubic incision; oophorectomy was performed through bilateral lumbar incisions. Oestrogens were given as an s.c. implant of a pellet containing 12 mg hexoestrol (Capomatic Tablets S4B; Boots Co. Ltd, Nottingham, England) through a small incision behind the left ear. The animals were killed under light ether anaesthesia by exsanguination via the axillary vessels. Half of the guinea-pigs which received hexoestrol were killed 1 week after implantation while the other half, along with the gonadectomized and the control animals, were killed 9 weeks later. Portions of spleen, lymph node, thymus, bone marrow, lulng, liver, kidney, heart, skeletal 19
muscle, adrenals, pancreas, brain and uterus were fixed in 4% formol saline. The tissues were processed routinely to paraffin, sections cut at 4 [km and stained with haematoxylin-eosin and periodic-acid-Schiff (PAS) stains. Gomori's reticulin and Perls' Prussian blue stains were used when necessary. The number of Foa-Kurloff cells in the alveolar area of the lungs and the number of Kupffer and Fob-Kurloff cells in the liver were estimated by counting 1000 nucleated cells in a number of randomly chosen fields of PASstained sections with an oil immersion lens. The figures were then expressed as percentage of the particular cell type per total nucleated cells. The significance of differences between mean values of groups was analysed by Student's t test. Specimens from the lung, liver and spleen were fixed for electron microscopy in 3% phosphate-buffered glutaraldehyde (pH 7.4) at 40, postfixed in Palade's 1 % osmium tetroxide and then embedded in Araldite. Sections were stained with lead citrate and examined in a Philips EM 400 electron microscope. RESULTS
Light microscopy The appearance of the Foa-Kurloff (FK) cells under the light microscope, their staining characteristics and distribution in the bone marrow, lymphoid organs and placenta of guinea pigs have been amply described (Ernstrom and Sandberg, 1971; Revell et al., 1971; Kortelainen and Korhonen, 1976b). A small number of FK cells was seen not only in the bone marrow, the thymus and the spleen, but also in the liver and lungs of female and to a lesser extent of male controls. Isolated FK cells were also seen in blood vessels of kidney, heart and skeletal muscle of the female but not the male controls. These cells completely disappeared from all organs after gonadectomy. In both sexes numerous FK cells were found in the bone marrow, the thymus and the spleen of guinea pigs receiving hexoestrol. In the spleen these cells were always lying in the red pulp but never in the white pulp. In the lymph nodes only a few isolated FK cells were seen in the subcapsular sinusoids and in the medullary sinuses. Slightly increased numbers of
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these cells were seen within vascular spaces of kidney, heart, skeletal muscle, adrenals, pancreas, brain and uterus. Ten weeks after hexoestrol administration complete atrophy of the thymic cortex was found, only medullary remnants surviving, including several Hassall's corpuscles. Numerous FK cells were seen in lymphatic and venous channels in and around the thymic remnants. These animals also showed signs of involution of the ymph node paracortex and the splenic white pulp, mainly round the postcapillary venules and the central arterioles respectively. The size of the characteristic PASpositive inclusion bodies varied, the smaller bodies- "young" FK cells-being found in the bone marrow and spleen of the animals killed 1 week after the implantation of hexoestrol as compared with those killed later. The mean percentage of FK and Kupffer cells per total nucleated cells in the liver and its variations in the different groups can be seen in Table I. Kupffer cells were significantly decreased in number after oophorectomy while no change was observed after orchidectomy. When hexoestrol was given for a period of 1 week the Kupffer cells were slightly increased in number in both sexes. However, the increase reached statistical significance only in the males (P
