Wednesday, January 16, 2013

The Birth of a Monocyte: Inflammatory Language No. 4

Monocyte by Asthydays 2012
Having only three days to live would be…daunting. I don’t suppose monocytes consider this, but once they enter the circulation, they have three days to either participate in inflammatory response reactions (be a reactionary) or die an oxidative death, only to be replaced by the next “frantic” monocyte. And so goes their life cycle.

Long before a monocyte is “born,” its ancestor or progenitor, a pluripotent stem cell, lives within bone marrow stromal cells and is capable of turning into any other kind of human cell: heart cell, liver cell, or a cell of the blood, to name a few. Some pluripotent stem cells develop into hematopoetic stem cells (HSC) that further develop into the blood cells of the human body—the lymphoid or myeloid cell lines. The myeloid cell line encompasses the platelets, red blood cells, mast cells, basophils, neutrophils, and eosinophils. It also encompasses monocytes, macrophages, and myeloid dendritic cells, leading to the birth of potential reactionaries.


From Wikipedia

In 1915, the movie The Birth of a Nation was released, triggering inflammatory responses all over the United States. Additionally, it became a recruitment tool for the KKK. The dangerous and faulty parallel between that movie and the monocyte is this: the monocyte can lead to inflammatory reactions, and the monocyte can recruit immune or reactionary cells. The parallel breaks down when there is no need to react, that it would be wrong and disease-causing to do so; so the tolerant monocyte just hangs out. There is no inflammation via its doing.

In the human, the majority of new monocytes are produced in the bone marrow of the vertebrae or sternum. In fetuses less than 4-5 months gestation, they are produced in the spleen and liver. Within a niche, a particular microenvironment of the bone marrow not yet determined, HSCs develop. This niche could be an osteoblastic (cell that builds bone) niche, an endothelial cell (lining of blood vessel) niche, a multipotent primitive mesenchymal cell (like CAR and nestin-expressing) niche in the stromal cells, or a combination of some or all of these.

From Wikipedia
Although the exact niche for HSC isn’t known, studies have revealed that CXCL12-CXCR4 (ligand-receptor) signaling is necessary for maintenance of HSC and their progenies. And, by influence of certain chemokines like interleukin-1 (IL-1), IL-3, IL-6, granulocyte-macrophage colony stimulating factor (GM-CSF), and stem cell factor (SCF), the myeloid cell line develops.

GM-CSF causes further differentiation (specialization) of the myeloid to a myeloblast, which is further differentiated into basophils, neutrophils, eosinophils, and monocytes. SCF, GM-CSF, IL-3 and IL-6, and specifically M-CSF aid in the development of promonoblasts, monoblasts, promonocytes, then finally—monocytes.

Macrophage: First Attempt by The Sensitive Scientist 2011 
The monocytes can reside within the marrow, be stored in the spleen, or nonchalantly patrol the blood for microbes—and await activation into macrophages or dendritic cells. If unchanged, the monocytes eventually die an apoptotic death. Their lack of DNA repair genes may have something to do with this for macrophages or dendritic cells are able to repair their DNA, and therefore live longer. I don’t suppose a monocyte considers this either, but it is their life.

Sources:

Apoptosis of monocyte: Bauer M, Goldstein M, Heylmann D, Kaina B (2012) Human Monocytes Undergo Excessive Apoptosis following Temozolomide Activating the ATM/ATR Pathway While Dendritic Cells and Macrophages Are Resistant. PLoS ONE 7(6): e39956. doi:10.1371/journal.pone.0039956

Bone marrow niches for HSC: Sugiyama T, NagasawaT ; Inf lamm Allergy Drug Targets. 2012 June; 11(3): 201–206. Published online 2012 June. doi:  10.2174/187152812800392689


There will be three Inflammatory Language posts devoted to monocytes. The first of which, Monocyte Fashion, addressed the style or types of monocytes. This post is the second devoted to monocytes. The third and forthcoming post will address cell trafficking, from the monocyte’s perspective. Future posts will eventually address the rest of Inflammatory Language, the song.

This is the fourth post of a series: Inflammatory Language. The series will briefly emphasize aspects of inflammation, mainly in response to microorganisms, but not always. You can contribute to this column by submitting a 300-500 word piece (or artwork) to me by email, along with byline. If deemed appropriate (it can be serious, political, scientific, or funny as long as it pertains to inflammation), we'll publish it here and the first place post (deadline February 28, 2013) will receive one copy of The Best Science Writing Online 2012 published by Scientific American/FSG!

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