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Equine September 2009 (Vol 4, No 7)

Abstract Thoughts—Cells Arising From Monocytes: Nature's Transformers

by David J. Hurley, PhD, James N. Moore, DVM, PhD

    Abstract*

    Dendritic cells have been considered an immune cell type that is specialized for the presentation of Ag to naive T cells. Considerable effort has been applied to separate their lineage, pathways of differentiation, and effectiveness in Ag presentation from those of macrophages. This review summarizes evidence that dendritic cells are a part of the mononuclear phagocyte system and are derived from a common precursor, responsive to the same growth factors (including CSF-1), express the same surface markers (including CD11c), and have no unique adaptation for Ag presentation that is not shared by other macrophages.

    Commentary

    George Orwell, who had a dark vision of a narrowly controlled world in 1984, might have been surprised to know that some toys made that year were so flexible that they had more than one use. In 1984, toy manufacturer Hasbro released the first generation of Transformers—toys that could be twisted and turned to change form (e.g., a single toy could become a car, plane, or robot). What a concept! One toy could have multiple functional fates, depending on the needs of the child in charge. As it turns out, Transformers have a lot in common with monocytes. (Perhaps screenplays for blockbuster monocyte movies are being considered in Hollywood right now.)

    The article by Hume that we cite below reminds us (particularly those who conduct research about antigen presentation and inflammation) that cells arising from monocytes are very fluid and plastic in their functional capacities, which can be freely interchanged in vivo. During the past 10 to 15 years, the ability to force monocytes along a pathway toward a specific functional role by exposing them to specific cytokines in culture has led researchers to think more about the function of monocyte-derived cells in initiating and regulating the immune response. Laboratory workers can turn monocytes into a homogeneous population of cells with well-defined functional activities that can be studied in vitro.

    Why did Dr. Hume feel the need to remind us that dendritic cells and macrophages are part of the same continuum of monocyte-derived cells? First, immunologists have been moving toward a new concept about how infections and vaccines induce immunity. Since the discovery that dendritic cells arise from monocytes with a distinctive morphology, a strongly expressed set of surface proteins that are associated with immune activation, and the ability to promote activation of T cells in culture systems, dendritic cells have been linked to the initiation of adaptive immunity. However, after careful analysis of the data, no one has identified cellular phenotypes or a specific family of unique cytokines that separate dendritic cells and the other families of functional macrophages into distinct cell populations. Second, the published "history" of studies involving macrophages over the past 3 decades indicates that macrophages can act as antigen-presenting cells and that the function of antigen presentation is not only the domain of dendritic cells.

    So why is Dr. Hume's article important to equine veterinarians? First, it means that you now have another grain of salt with which to analyze the claims being made about vaccines and immune modulators. If the fate of monocytes is plastic rather than fixed, this may help account for the short-term effects of these types of products. Second, a horse's preexisting inflammatory state, environmental inflammatory and immune stimuli, and stress level all affect the strength and duration of immune responses to these products.

    As you might expect, there is good news and bad news in all of this. On the positive side, horses have lots of "players" (essentially, all the cells that arise from monocytes) that can enhance a veterinarian's attempt to arm the adaptive immune system and provide protection against disease. The bad news is that these players can be recruited to tissue and ordered to differentiate into cells with primary functions of managing microbial invasions and coordinating the repair of damaged tissue. These activities can keep these players from presenting antigen and promoting further development of adaptive immunity. Overall, it means that the interactive system of control over the function of monocytes is in the "hands" of the cells in tissue. Thus, the tissue must be in charge of the overall outcome of how monocytes function.

    Thus, monocytes are the ultimate "transformers" in nature. They sense the needs of the body by responding to the myriad signals released from individual cells in tissue and differentiating, as needed, to one of several functional forms. These forms support systems that control invaders and repair tissue damage by invaders and that drive long-term responses to invaders so that subsequent interaction will end more favorably for the body.

    Monocytes not only are transformers but also are like people in Hollywood, whom Andy Warhol described as follows: "They're beautiful. Everybody's plastic, but I love plastic. I want to be plastic." Monocytes are plastic in regard to their adaptability: they change form and function to serve the body over their relatively long lifetime. As Wayne Dyer, self-help author and speaker, said, "Transformation literally means going beyond your form." By this definition, monocytes certainly undergo transformation.

    *Reprinted verbatim from Hume DA. Macrophages as APC and the dendritic cell myth. J Immunol 2008;181:5829-5835; with permission from Elsevier.

    NEXT: Clinical Snapshot — Dysphagia and Nasal Discharge in a Quarter Horse Gelding

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