After maturing in the bone marrow, neutrophils and monocytes enter the blood and circulate throughout the body. Although these cells can perform some phagocytic functions within the blood, their main functions, including phagocytosis and destruction of microbes and dead tissue cells, take place in extravascular sites of infection virtually anywhere in the body.
Blood neutrophils and monocytes are recruited to tissue sites of infection and injury by a selectin-, integrin-, and chemokine-dependent multistep process, which follows the basic sequence common to the migration of all leukocytes into tis sues, discussed earlier. As we will consider in detail in Chapter 4, neutrophils are usually the most numerous type of leukocyte to accumulate in tissues, within 24 to 48 hours after the onset of an infection or injury, and are then replaced by monocytes. The early predominance of neutrophils probably reflects the fact that there are many more of these cells in the blood and they may respond more rapidly to chemokines compared to monocytes or other leukocytes. After entering tissues, neutrophils have short life spans before dying by apoptosis, whereas monocytes survive longer and may also proliferate in the tis sues. However, in some inflammatory sites, neutrophils are not recruited at all, unlike monocytes. These different migratory behaviors likely reflect variations in relative expression of adhesion molecules and chemokine receptors on neutrophils versus monocytes. Neutrophils express CXCR1 and CXCR2, which bind CXCL1 and CXCL8 (IL-8), the major chemokines with ELR motifs that support neutrophil migration into tissues (see Table 1). Early neutrophil recruitment is a consequence of early and abundant CXCL8 production by tissue-resident macrophages and other cells in response to infections. In contrast to neutrophils, classical monocytes, which are the main type of monocyte recruited to inflammatory sites, express CCR2. This receptor binds several chemokines, the most important one for monocyte recruitment being CCL2 (MCP 1). Thus, monocyte recruitment occurs when resident tissue cells produce CCL2 in response to an infection.
Table1. Selected Chemokines and Chemokine Receptors
