Page 1096 - Williams Hematology ( PDFDrive )

1070 Part VIII: Monocytes and Macrophages Chapter 67: Structure, Receptors, and Functions of Monocytes and Macrophages 1071

Glut-1 Figure 67–23. Hypoxia induces marked changes in the pheno-
type of macrophages. Macrophages upregulate hypoxia-inducible
Mitogens CXCR4 transcription factor (HIF)-1 and HIF-2 in hypoxia, which translocate to
• IL-6 the nucleus to induce the expression of a wide array of target genes.
• HGF Tie-2 Angiogenesis Several important cell-surface receptors are upregulated in hypoxia,
• PDGF FIFs-1 • VEGF including the glucose receptor GLUT-1 (for increased glucose uptake
•FGF2 HIFs-2 • FGFS 1 & 2 as the cell switches to anaerobic glycolysis to make ATP in the absence
• VEGF • PDGF of oxygen), the chemokine stromal cell-derived factor-1 (SDF-1) recep-
• MIF • IL-8 tor CXCR4, and the angiopoietin receptor Tie-2. Hypoxia also stimulates
• TF the expression of a wide array of other protumor cytokines, enzymes,
• COX-2 and receptors, grouped here according to their known function in
Invasion • MMP-7 tumors. Downregulation of a factor or tumor-associated macrophage
and metastasis • Pleiotrophin function is indicated by an arrow. Ag, antigen; COX, cyclooxygenase;
• TF • Angiotrophin-1 FGF, fibroblast growth factor; HGF, hepatocyte growth factor; MIF, mac-
• Leptin
• MMP-7 rophage migration inhibitory factor; MMP, matrix metalloproteinase;
• uPA/R Immunosuppression • Fibronectin PDGF, platelet-derived growth factor; PGE , prostaglandin E ; TF, tissue
2
2
• MIF • IL-10 • Magic roundabout factor; uPA/R, urokinase-type plasminogen activator receptor; VEGF,
• PGE2 vascular endothelial growth factor. (Modified with permission from
phagocytosis, Lewis CE, Hughes R: Inflammation and breast cancer. Microenvironmental
Ag presentation factors regulating macrophage function in breast tumours: hypoxia and
(via inhibition of CD80)
angiopoietin-2. Breast Cancer Res 2007;9(3):209.)

acutely and following persistent injury, to chronic inflammation. Stor- analysis of macrophage functions within their native hematopoietic
age of poorly degraded materials in lysosomes, for example, results in tissue environment. A deeper understanding of macrophage physio-
sustained production of degradation products, whereas massive, acute logic functions and of their role in a broad range of diseases should
responses have a profound impact on the systemic circulation, endo- lead to the development of fresh insights into the pathogenesis and
crine and nervous systems, and on metabolic pathways. Short-range management of hematologic disorders.
interactions include giant cell formation during granulomatous inflam-
mation, and also contact-dependent immunoregulation by surface mol-
140
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