Page 1070 - Williams Hematology ( PDFDrive )

1045

CHAPTER 67 degradation, with emphasis on membrane flow and secretion. These pioneer-

STRUCTURE, RECEPTORS, ing studies culminated in the discovery of dendritic cells as potent, specialized
antigen-presenting cells. Subsequent development of monoclonal antibodies
AND FUNCTIONS OF and molecular cloning of surface proteins and cytokines, followed by microar-
ray analysis and genomics, provided the sensitive and specific tools to analyze
MONOCYTES AND macrophage functions in vitro and in vivo. These studies have brought insights
into macrophage cytotoxic and antimicrobial activities and, to a lesser extent,
their trophic, homeostatic functions in the body. Macrophages play a major
MACROPHAGES role in innate as well as adaptive immunity.

Steven D. Douglas and Anne G. Douglas MONONUCLEAR PHAGOCYTE SYSTEM
OVERVIEW
SUMMARY
Modern study of mammalian phagocytes began with Metchnikoff in the
The monocyte is a spherical cell with prominent surface ruffles and blebs 19th century. An understanding of the ontogeny, kinetics, and function
when examined by scanning electron microscopy. As the monocyte enters the of phagocytic cells in animals led to the concept of the mononuclear
phagocyte system. Kinetic studies indicate that marrow monoblasts
1,2
tissue and differentiates into a macrophage, the cell volume and number of and monocytes develop from the common myeloid progenitor, a deriva-
cytoplasmic granules increase. Cell shape varies, depending on the tissue in tive of the hematopoietic stem cell, and that tissue macrophages develop
which the macrophage resides (e.g., lung, liver, spleen, brain). A characteristic from monocytes that have migrated from the blood pool in response
feature of macrophages is their prominent electron-dense membrane-bound to chemotactic stimuli (Table 67-1 and Chap. 18). Tissue macrophages
lysosomes, which can be seen fusing with phagosomes to form secondary lys- share many functional characteristics, such as phagocytic and microbial
osomes. The latter contain ingested cellular and noncellular material in differ- killing capabilities and adherence to glass or plastic surfaces in vitro.
ent stages of degradation. A broad range of surface receptors for many ligands, Vascular endothelium, reticular cells, and dendritic cells of lymphoid
including the Fc portion of immunoglobulin, complement proteins, cytokines, germinal centers usually are not included in the mononuclear phago-
3
chemokines, lipoproteins, and others, are on the cell surface. Macrophages cyte system, although the now obsolete term reticuloendothelial system
differ in appearance, biochemistry, and function based on the environment denoted those cells as playing some complementary part with mono-
in which they mature from monocytes. These differences are exemplified by nuclear phagocytes. In addition to developing the multitude of types of
tissue macrophages, monocytes can differentiate into myeloid-derived
the diversity among dendritic cells of lymph nodes, histiocytes of connective dendritic cells. 4,5
tissue, osteoclasts of bone, Kupffer cells of liver, microglia of the central ner-
vous system, and macrophages of the serosal surfaces, each fashioned to meet
the local needs of the mononuclear phagocyte system, which plays a role in STRUCTURE
inflammation and host defense against microbes. Modern cell biologic meth- The blood monocyte is a medium to large motile cell that can mar-
ods refined our knowledge of surface receptors, endocytosis, and lysosomal ginate along vessel walls and has a propensity for adherence to sur-
faces. Monocytes respond to inflammation and chemotactic stimuli
by active diapedesis across vessel walls into inflammatory foci, where
they can mature into macrophages, with greater phagocytic capacity
and increased content of hydrolytic enzymes. Free macrophages also
are present in mammary glands, alveolar spaces, pleura, peritoneum,
Acronyms and Abbreviations: APC, antigen-presenting cell; CD, cluster of and synovia. The somewhat less-motile fixed-tissue macrophages are
differentiation; CR, complement receptor; CSF, colony-stimulating factor; found in different tissues and serous cavities. The functions of mononu-
DC, dendritic cell; EGF, epidermal growth factor; EGF-TM7, epidermal growth clear phagocytes include phagocytosis, killing, and digestion of micro-
factor–seven transmembrane; EMR2, epidermal growth factor–like module organisms, particulate material, or tissue debris; secretion of chemical
containing mucin-like hormone receptor–like 2; FcR, Fc receptor; GM-CSF, mediators and regulators of the inflammatory response; interaction (as
granulocyte-monocyte colony-stimulating factor; GPCR, G-protein–coupled dendritic cells) with antigen and lymphocytes in the generation of the
receptor; HLA, human leukocyte antigen; IBD, inflammatory bowel disease; immune response; cytotoxicity, such as killing of some tumor cells; and
IFN, interferon; Ig, immunoglobulin; IL, interleukin; IMP, intramembrane other functions specific for macrophages of particular tissues.
particle; IRAK, interleukin receptor-associated kinase; LFA, lymphocyte The development of techniques to isolate monocytes from blood
function–associated antigen; LPS, lipopolysaccharide; m-φ, macrophage; of adult human subjects led to the discovery that monocytes are hetero-
MARCO, macrophage receptor with collagenous structure; M-CSF, macro- geneous with regard to cell volumes. Isolation of purified monocytes by
adherence to glass substrates or to gelatin-coated flasks or by centrifugal
phage colony-stimulating factor; MHC, major histocompatibility complex; elutriation reveals distinct populations of monocytes. In addition to
1,2
MPO, myeloperoxidase; NF, nuclear factor; NLR, NOD-like receptor; NOD, the usual 12- to 15-μm diameter (when measured on a dried blood film)
nucleotide-binding oligomerization domain; PI3K, phosphatidylinositol monocyte, so-called regular monocytes, a somewhat smaller cell that is
3-kinase; PS, phosphatidylserine; SR, scavenger receptor; TGF, transforming less active than its larger, more mature counterpart has been identified.
growth factor; TLR, toll-like receptor. This cell is referred to as a small immature monocyte, but its functional
significance is not clear.

Kaushansky_chapter 67_p1043-1074.indd 1045 9/21/15 10:42 AM