The origin of mononuclear phagocytes

During ontogeny, the hematopoietic stem cell - a cell of mesenchymal origin - arises in the yolk sac. In a later stage of gestation, these cells migrate to the fetal liver, where immature mononuclear phagocytes develop; hematopoiesis in the liver does not cease until term or the second week after birth, depending on the species. Soon after hematopoiesis begins in the fetal liver, monocytes appear in the circulation; only after that does hematopoiesis commence in the bone marrow. Before hematopoiesis commences in the bone marrow, osteoclasts formed by fusion of circulating mononuclear phagocytes (e.g. monocytes or younger cells of this cell line) are found in embryonic bone. The approximate time during gestation, when mononuclear phagocytes appear in hematopoietic organs and in the circulation of mouse and human, is shown in Table 1.

In adult life, mononuclear phagocytes are present in all tissues, but under normal conditions proliferating mononuclear phagocytes occur only in the bone marrow. The most immature cell of the mononuclear phagocyte cell line present in the bone marrow is the monoblast. This cell is derived from a granulocyte-monocyte progenitor cell which can be considered to be a committed stem cell that is derived from the multipotent hematopoietic stem cell. Division of the monoblast gives rise to two promonocytes, and the two daughter cells of a promonocyte are monocytes.

Thus, in the bone marrow from monoblast to monocytes, there is a cell amplification of four times. Monocytes remain in the bone marrow for only a short time (less than 24 h) and then enter the circulation, where they are present in a circulating or marginating pool. The marginating monocytes migrate through the endothelium of the vessel wall to the various tissues and body cavities. Adhesion molecules on monocytes and on endothelial cells, together with chemotatic factors, are involved in the migration of monocytes from the blood vessels into the tissues or body cavities.

In the extravascular tissues, monocytes transform into (exudate) macrophages. In the lungs, for example, monocytes differentiate directly into alveolar macrophages without maturation in the interstitium; in the sinusoids of the liver, monocytes become the Kupffer cells; and in the peritoneal cavity, monocytes arrive directly from the capillaries or via the milky spots in the omentum. In normal tissues, only a very small percentage of macrophages divide, these macrophages also having recently originated from the bone marrow. Little is known about the ultimate fate of the macrophages. Since there is no evidence that macrophages recirculate via the lymph vessels to the circulation, it seems likely that they die in the tissues where they reside or migrate to local lymph nodes.

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