Most white blood cells function in tissues other than the blood; blood simply transports them to where they are needed. A local infection or injury in any tissue rapidly attracts white blood cells into the affected region as part of the inflammatory response, which helps fight the infection or heal the wound (Movie 22.3).
The inflammatory response is complex and is governed by many different signal molecules produced locally by mast cells, nerve endings, platelets, and white blood cells, as well as by the activation of complement (discussed in Chapter 24). Some of these signal molecules act on the endothelial lining of nearby capillaries, helping white blood cells to first stick and then make an exit from the bloodstream into the tissue where they are needed, as described in Chapter 19 (see Figure 19–28 and Movie 19.2). Damaged or inflamed tissues and local endothelial cells secrete other molecules called chemokines, which act as chemoattractants for specific types of white blood cells, causing them to become polarized and crawl toward the source of the attractant. As a result, large numbers of white blood cells enter the affected tissue (Figure 22–28).
Other signal molecules produced during an inflammatory response escape into the blood and stimulate the bone marrow to produce more leukocytes and release them into the bloodstream. The regulation tends to be cell-type specific: some bacterial infections, for example, cause a selective increase in neutrophils, while infections with some protozoa and other parasites cause a selective increase in eosinophils. (For this reason, physicians routinely use differential white blood cell counts to aid in the diagnosis of infectious and other inflammatory diseases.)
In other circumstances, erythrocyte production is selectively increased—for example, in response to anemia (lack of hemoglobin) due to blood loss, and in the process of acclimatization when one goes to live at high altitude, where oxygen is scarce. Thus, blood cell formation, or hematopoiesis, necessarily involves complex controls, which regulate the production of each type of blood cell individually to meet changing needs.
Figure 22–28 Chemotaxis of white blood cells to damaged tissue.
a chemoattractive signal released from a site of damage, which is toward the bottom of the page, causes white blood cells to exit from the capillary by crawling between adjacent endothelial cells, as shown.
megakaryocyte process budding off platelets endothelial cell of sinus wall bone marrow Contains multipotent hematopoietic Stem Cells, able to Give Rise to all Classes of blood Cells
In the bone marrow, the developing blood cells and their precursors, including the stem cells, are intermingled with one another, as well as with fat cells and other stromal cells (connective-tissue cells), which produce a delicate supporting meshwork of collagen fibers and other extracellular matrix components. In addition, the whole tissue is richly supplied with thin-walled blood vessels, called blood sinuses, into which the new blood cells are discharged. Megakaryocytes are also present; these, unlike other blood cells, remain in the bone marrow when mature and are one of its most striking features, being extraordinarily large (diameter up to 60 μm) with a highly polyploid nucleus. They normally lie close beside blood sinuses, and they extend processes through holes in the endothelial lining of these vessels; platelets pinch off from the processes and are swept away into the blood (Figure 22–29 and Movie 22.4).
Because of the complex arrangement of the cells in bone marrow, it is difficult to identify in ordinary tissue sections any but the immediate precursors of the mature blood cells. There is no obvious visible characteristic by which we can recognize the ultimate stem cells. In the case of hematopoiesis, the stem cells were first identified by a functional assay that exploited the wandering lifestyle of blood cells and their precursors.