Journal of cell science. Supplement. 1988;9:1.
Plasma membrane receptors control macrophage activities such as growth, differentiation and activation, migration, recognition, endocytosis and secretion. They are therefore important in a wide range of physiological and pathological processes including host defence, inflammation and repair, involving all systems of the body including the arterial wall and nervous system. The versatile responsiveness of these cells to various stimuli depends on their ability to express a large repertoire of receptors, some restricted to macrophages and closely related cells, others common to many cell types. This volume contains reviews of the macrophage receptors that are best characterized and deals with aspects of signal transduction and function of the actin cytoskeleton. Our introduction is designed to place these topics in perspective. We summarize features of constitutive and induced mononuclear phagocyte distribution within the body and consider receptor expression and macrophage responses in the context of cell heterogeneity associated with its complex life history. We classify receptors discussed in detail in other chapters, list ligand-binding properties that are not as well defined, and briefly review general features of receptor function in macrophages. An understanding of macrophage receptor biology should bring insights into the contribution of these cells to physiology and disease and result in an improved ability to manipulate activities within the mononuclear phagocyte system.
Current Rheumatology Reports [Internet]. 2012 Aug 2 [cited 2012 Aug 3];
Macrophages play a central role in the pathogenesis of rheumatoid arthritis (RA). There is an imbalance of inflammatory and antiinflammatory macrophages in RA synovium. Although the polarization and heterogeneity of macrophages in RA have not been fully uncovered, the identity of macrophages in RA can potentially be defined by their products, including the co-stimulatory molecules, scavenger receptors, different cytokines/chemokines and receptors, and transcription factors. In the last decade, efforts to understand the polarization, apoptosis regulation, and novel signaling pathways in macrophages, as well as how distinct activated macrophages influence disease progression, have led to strategies that target macrophages with varied specificity and selectivity. Major targets that are related to macrophage development and apoptosis include TNF-α, IL-1, IL-6, GM-CSF, M-CSF, death receptor 5 (DR5), Fas, and others, as listed in Table 1. Combined data from clinical, preclinical, and animal studies of inhibitors of these targets have provided valuable insights into their roles in the disease progression and, subsequently, have led to the evolving therapeutic paradigms in RA. In this review, we propose that reestablishment of macrophage equilibrium by inhibiting the development of, and/or eliminating, the proinflammatory macrophages will be an effective therapeutic approach for RA and other autoimmune diseases. Table 1 Novel macrophage-related therapeutic agents for rheumatoid diseases Agent Mechanisms Development phase Reference Antihuman DR5 antibody, TRA-8(CS-1008) Induces apoptosis of targeted cells Preclinical [27••] Tumor necrosis factor-converting enzyme (TACE) inhibitors, TMI-005 and BMS-561392 Inhibits the release of soluble TNF from its membrane-bound precursor Clinical Phase II  GM-CSF and GM-CSF receptor antibodies Blocks the binding of GM-CSF to its receptor and downstream signaling Clinical Phase II [3, 11••] JAK inhibitor, Tofacitinib and Ruxolitinib Abrogated TNF-induced STAT1 activation and expression of genes encoding inflammatory chemokines Clinical Phase III  Tyrosine kinase inhibitor, Imatinib and mastinib Inhibits tyrosine kinases, including platelet-derived growth factor receptor (PDGFR), Kit, and Fms related kinases Clinical Phase II-III [52, 53] Anti-IL-12/IL-23 monoclonal antibody, ustekinumab Blocking binding of IL-12/23 to their receptors and the downstream signaling Approved for psoriasis and psoriatic arthritis  Clodronate liposomes Deplete synovial macrophages by intraarticular administration Open study in patients who were scheduled for knee joint replacement .
Springer Seminars in Immunopathology. 1982;5(2):161–74.
[toggle_content title=”Abstract”] The propensity of malignant neoplasms to produce metastases in organs distant from the primary site is the principal cause of failure in the treatment of cancer. There are several reasons for the present lack of success in treating metastatic disease. First, at the time of diagnosis and excision of primary tumors, metastasis may have already occurred and the lesions are often too small to be detected. Moreover, widespread dissemination of metastases frequently takes place before symptoms of disease occur. Second, the anatomic location of many metastases may limit the effective dose of therapeutic agents that can be delivered to the lesions without being toxic to normal tissues or the host. The third, and most formidable problem, is that the phenotypic diversity of tumor cells in a single neoplasm is sufficiently great that the response of cells in metastatic lesions to therapy may differ from cells in the primary tumor, and individual metastases within the same patient may also respond differently to therapy [reviews, 12, 14, 41]. This problem means that successful treatment of metastatic disease will require the development of therapeutic regimens that can circumvent the cellular heterogeneity found in tumors and against which resistance is unlikely to develop. The role of macrophages in host defense against neoplasms has attracted increasing attention over the last few years [reviews, 4, 17, 39, 60]. This’stems in part from the disappointing results obtained in recent clinical efforts to augment host resistance to tumors by specific immunotherapy. In addition, there is a growing body of experimental evidence that macrophages are important effector cells in host defense against tumors and metastatic tumors in particular [review, 17]. Most important, activated tumoricidal macrophages are able to kill phenotypically diverse tumor cells, including cells that are resistant to killing by other components of the host defense system and various anticancer drugs [review, 17]. In this chapter we present a brief summary of current knowledge about the role of activated macrophages in host defense against metastasis and describe aspects of work done in our laboratories over the last few years using liposome-encapsulated macrophage activation agents to augment host resistance to metastatic tumors. [/toggle_content]