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why does a red blood cell not have a nucleus

Shown to be in mice rats (and sick humans), the cell-cell interaction between a macrophage (this is a big engulfing cell required for immunity) and young red blood cells (RBC), is known as the erythroblastic island (commonly known as EBI). If you googled it, there is a scientific review in 2008 that describes this structure. At the embryonic stage (in humans), we still retain our RBC nuclei. But as we developed into fetus and adult, we no longer have RBC nuclei. This is thought to be related to the EBI present (in the fetal liver and adult bone marrow respectively). Currently, there is a lack of information of the EBI in other mammals. The only proven ones are mice, rats and sick humans. It is widely assumed (not proven) that mammals have EBIs. Besides mammals, some other animals (e. g. birds) have enucleated RBC, and some don't. It is unclear why is it so. Our lab thinks that it might be related to the formation of the EBI. In addition to engulfing the RBC nuclei, it is believed that the macrophage acts as a "nurse" cell as proposed in the 50s. In other words, possibly providing iron, and possibly providing some proteins required for young RBC to mature. In early 2013, for the first time, it was showed that these macrophages are important in animal models (published by 2 research groups in nature medicine journal).

As for enucleation (the removal of erythroid nuclei), the exact mechanisms are unknown. But cytoskeleton proteins are important players in enucleation. However, there isn't enough information, as these proteins are essential for other important cellular activities as well. For example, bringing in nutrients, development and cellular migration. Most animal models that lack these proteins are unavailable for studies, and these animals usually die at the embryonic stage. The research mentioned by EdoDodo is a proposed model on how enucleation takes place, and is a widely accepted model. Currently, our lab are working on another model that could partially explain how enucleation is being triggered. In addition to better oxygen diffusion across the membranes, some older scientific papers mentioned that it lightened the cardiac workload. Each extruded RBC nuclei is approximately 40 picograms. A normal healthy adult individual would produce about 2 million RBC per second. That would be 0. 08 milligrams of weight per second are required to be removed. However, I couldn't trace the scientific evidence for this claim, but this have been cited by some scientific papers. The other advantage would be to reduce risk of hemolysis when transversing through the microvasculature. In other words, mature RBC can move along tiny blood capillaries by changing their biconcave shape (to bell-shaped I think), so that they will not rupture (and die).

Also, not all RBCs have similar shapes and sizes. You might want to google it for more information. I think camels have slightly different RBC morphology.
February 10, 2008 Tags: CAMBRIDGE, Mass. Б Unlike the rest of the cells in your body, your red blood cells lack nuclei. That quirk dates back to the time when mammals began to evolve. Other vertebrates such as fish, reptiles and birds have red cells that contain nuclei that are inactive. Losing the nucleus enables the red blood cell to contain more oxygen-carrying hemoglobin, thus enabling more oxygen to be transported in the blood and boosting our metabolism. б Scientists have struggled to understand the mechanism by which maturing red blood cells eject their nuclei. Now, researchers in the lab of Whitehead Member have modeled the complete process in vitro in mice, reporting their findings in Nature Cell Biology online on February 10, 2008. The first mechanistic study of how a red blood cell loses its nucleus, the research sheds light on one of the most essential steps in mammalian evolution. It was known that as a mammalian red blood cell nears maturity, a ring of actin filaments contracts and pinches off a segment of the cell that contains the nucleus, a type of Бcell division.

Б The nucleus is then swallowed by macrophages (one of the immune systemБs quick-response troops). The genes and signaling pathways that drive the pinching-off process, however, were a mystery. БUsing a cell-culture system we were actually able to watch the cells divide, go through hemoglobin synthesis and then lose their nuclei,Б says Lodish, who is also a professor of biology at Massachusetts Institute of Technology. БWe discovered that the proteins Rac 1, Rac 2 and mDia2 are involved in building the ring of actin filaments. Б БRac 1 and Rac 2 were involved in disposing the nuclei of red blood cells,Б says Peng Ji, lead author and postdoctoral researcher in the Lodish lab. БThese proteins are known for their role in creating actin fibers in many body cells, and a necessary component of many important cellular functions including cell division that support cell growth. Б His cell-culture system began with red blood cell precursors drawn from an embryonic mouse liver (in mammalian embryos, the liver is the main producer of such cells, rather than bone marrow as in adults). The cultured cells, synchronized to develop together, divided four or five times before losing their nuclei and becoming immature red blood cells. б The researchers used fluorescence-based assays that enabled them to probe the changes in the red blood cells through the different stages leading up to the loss of the nucleus.

The researchers plan to further investigate the entire process of red blood cell formation, which may lead to insights about genetic alterations that underlie certain red blood cell disorders. БDuring normal cell division, each daughter cell receives half the DNA,Б comments Lodish. БIn this case, when the red blood cell divides, one daughter cell gets all the DNA. WhatБs fascinating is that in this case, that daughter cell gets eaten by macrophages. Until now, scientists were unable to study these cells because they were unable to see them. Б The research was supported by the National Institutes of Health and Amgen, Inc. Harvey Lodish's primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also a professor of biology at Massachusetts Institute of Technology. Full Citation: Nature Cell Biology, Volume 10, Number 3 Authors: Peng Ji (1), Senthil Raja Jayapal (1,2) and Harvey Lodish (1) (1) Whitehead Institute for Biomedical Research, Cambridge, MA (2) Stem Cell Group, 4, Genome Institute of Singapore #08-01, Genome, 60 Biopolis Street, Singapore 138672

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