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Biomedical subjects

R van Furth

Publications and source records attributed to R van Furth.

At least 271 records · Page 15Linked to original sources

Kinetic analysis of the growth of bone marrow mononuclear phagocytes in long-term cultures.

The present work concerns a mathematical analysis of the growth of monoblasts, promonocytes, and macrophages in long-term bone marrow cultures in the presence of conditioned medium. For this purpose, use was made of the normalized data of four experiments, each done in triplicate. The computer program was based on a concept of hypothetical subcompartments within each developmental stage. The growth parameters were then determined experimentally or by trial and error after a series of computer simulations. The mathematical results are in close agreement with the numbers of monoblasts, promonocytes, and macrophages obtained by counts in 21-day-old bone marrow cultures. This approach provides a means to understand the kinetic behaviour of mononuclear phagocytes.

Animals↗

Presence of the factor increasing monocytopoiesis (FIM) in rabbit peripheral blood during an acute inflammation.

An intraperitoneal injection of latex in rabbits was found to give rise to an increase in the number of macrophages at the site of inflammation and a concomitant monocytosis in the peripheral blood. The results showed that during the initial phase of the inflammatory reaction a humoral factor is present in the circulation of these animals that stimulates the monocyte production in the bone marrow in a concentration-dependent way. This factor has been called the factor increasing monocytopoiesis (FIM), in analogy with the name given to the factor previously found in mice. Rabbit FIM is cell-line specific since it has no effect on granulocyte or lymphocyte production, has an estimated molecular weight of between 10,000 and 25,000 daltons, was found to be sensitive to treatment with proteases, to be unaffected by glycosidases, and to be readily inactivated in vitro at 37 degrees C. Neither rabbit nor mouse FIM is species specific, since rabbit FIM evoked moderate monocytosis in mice and vice versa.

Animals↗

A quantitative evaluation of pulmonary macrophage kinetics.

A new mathematical approach to the calculation of the kinetics of macrophages in a tissue compartment is presented. This approach, which takes into account the influx of monocytes into the compartment, the local division of mononuclear phagocytes, and the efflux of macrophages from the compartment, was applied to data on the pulmonary macrophages of mice in the normal steady state. The results show that at least 70% of the pulmonary macrophage population is supplied by monocyte influx and at most 30% by local division of immature mononuclear phagocytes originating from the bone marrow. The calculated turnover time of pulmonary macrophages is about 6 days, and the turnover amounts to 14.6 X 10(3) macrophages/hr.

Animals↗

In vitro formation of osteoclasts from long-term cultures of bone marrow mononuclear phagocytes.

The origin of osteoclasts was studied in an in vitro model using organ cultures of periosteum-free embryonic mouse long-bone primordia, which were co-cultured with various cell populations. The bone rudiments were freed of their periosteum-perichondrium by collagenase treatment in a stage before cartilage erosion and osteoclast formation, and co-cultured for 7 d with either embryonic liver or mononuclear phagocytes from various sources. Light and electron microscopic examination of the cultures showed that mineralized matrix-resorbing osteoclasts developed only in bones co-cultured with embryonic liver or with cultured bone marrow mononuclear phagocytes but not when co-cultured with blood monocytes or resident or exudate peritoneal macrophages. Osteoclasts developed from the weakly adherent, but not from the strongly adherent cells of bone marrow cultures, whereas 1,000 rad irradiation destroyed the capacity of such cultures to form osteoclasts. In bone cultures to which no other cells were added, osteoclasts were virtually absent. Bone-resorbing activity of in vitro formed osteoclasts was demonstrated by 45Ca release studies. These studies demonstrate that osteoclasts develop from cells present in cultures of proliferating mononuclear phagocytes and that, at least in our system, monocytes and macrophages are unable to form osteoclasts. The most likely candidates for osteoclast precursor cells seem to be monoblasts and promonocytes.

Animals↗

Comparison of the in vivo and in vitro proliferation of monoblasts, promonocytes, and the macrophage cell line J774.

Mononuclear phagocytes are localized in the bone marrow compartment (monoblasts, promonocytes and macrophages), the circulation (monocytes), and the tissues and serous cavities (macrophages). In vivo and in vitro studies done in murine bone marrow have shown that monoblasts and promonocytes are the most immature, dividing cells of the mononuclear phagocyte cell line; monocytes and resident macrophages do not divide. A very small percentage of the mononuclear phagocytes in the tissues, which are bone-marrow derived and have already the morphology of macrophages, divide once in vivo. The progeny of these dividing cells contribute to the maintenance of the tissue population of macrophages under steady-state conditions. In vitro an appreciable percentage of (young) macrophages divide, in all probability due to the influence of colony-stimulating factor. The cells of macrophage cell lines are transformed cells that proliferate continuously. The morphological, cytochemical and functional characteristics of all these kinds of cells, as well as their proliferative behavior in vivo and in vitro, show great similarity, although there are also distinct differences.

Bone Marrow↗

The role of bacterial adherence in the pathogenesis of infective endocarditis.

Bacterial adherence as a result of specific surface properties may be a contributory factor in the pathogenesis of bacterial endocarditis giving certain types of bacteria a selective advantage to cause this disease. Adherence could interact with other pathogenetic mechanisms, and this interaction could promote or hamper the development of endocarditis. Dextran production by streptococci, the activation of the clotting system by monocyte tissue thromboplastin, and phagocytic removal of bacteria from the vegetational surface by granulocytes and monocytes are examples of interacting mechanisms that could contribute to the pathogenesis of bacterial endocarditis.

Adhesiveness↗

The origin of pulmonary macrophages.

The controversy as to whether pulmonary macrophages derive from monocytes or from precursor cells in the pulmonary interstitium has been solved by quantitative analysis of 3H-thymidine labeling data on the circulating monocytes and the total population of pulmonary macrophages isolated from mice by lavage and enzyme digestion of lung tissue. It was found that in the normal steady state, during acute inflammatory reactions, and under long-term corticosteroid treatment, pulmonary macrophages derive mainly from circulating monocytes which enter the lungs and become pulmonary macrophages within a few hours. Local division of pulmonary macrophages made only a minor contribution to the maintenance of the population; a dividing precursor cell population located in the interstitium of the lung could not be demonstrated. The few mononuclear phagocytes dividing locally in the lung have most probably arrived recently from the circulation and originate in the bone marrow. These dividing cells already have the characteristics of pulmonary macrophages.

Animals↗

In vitro proliferation of mononuclear phagocytes from murine and human bone marrow.

Techniques for liquid culture of proliferating mononuclear phagocytes from bone marrow of mice and men are described. Mouse bone marrow must be cultured in the presence of colony-stimulating factor, whereas proliferation of human mononuclear phagocytes occurred in medium with 50% serum but without colony-stimulating factor. The number of mononuclear phagocytes that can be determined in mouse bone marrow cultures is higher than that in cultures of human bone marrow. However, the number of mononuclear phagocytes found for the human system is an underestimation, because the immature mononuclear phagocytes cannot be recognized at the light-microscopical level. These precursor cells (monoblasts and promonocytes) can be recognized with the electron microscope. The characteristics of the various types of mononuclear phagocyte, especially in cultures of murine bone marrow, are reviewed.

Animals↗