Riding on the red road: Red blood cells are also known as RBCs, red cells, red blood corpuscles (an archaic term), haematids, erythroid cells or erythrocytes (from Greek erythros for "red" and kytos for "hollow", with cyte translated as "cell" in modern usage).
These cells' cytoplasm is rich in haemoglobin, an iron-containing biomolecule that can bind oxygen and is responsible for the blood's red color.
As red blood cells contain no nucleus, protein biosynthesis is currently assumed to be absent in these cells, although a recent study indicates the presence of all the necessary biomachinery in the cells to do so.
In humans, mature red blood cells are oval and flexible biconcave disks. They lack a cell nucleus and most organelles to accommodate maximum space for haemoglobin. 2.4 million new erythrocytes are produced per second. The cells develop in the bone marrow and circulate for about 100–120 days in the body before their components are recycled by macrophages. Each circulation takes about 20 seconds. Approximately a quarter of the cells in the human body are red blood cells.
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| Scanning electron micrograph of blood cells. From left to right: human erythrocyte, thrombocyte (platelet), leukocyte. |
RBCs are specialized bags of hemoglobin Red blood cells are designed to pick up oxygen from the lungs and
release it into the tissues of the body. This is their major function. The
only reason that they can pick up and carry oxygen around is because they contain a
protein within them called hemoglobin.
If red blood cells (RBCs, or erythrocytes) have to carry oxygen, yet
it is the hemoglobin inside them that carries the oxygen, we might expect that RBCs
should be loaded with hemoglobin. And in fact, they are! They load themselves up
so much with hemoglobin to carry oxygen that their nuclei get in the way. So, RBCs
don't have any nuclei! 1/3 of their entire volume is due to hemoglobin!
Production of RBCs: This process is called erythropoiesis. Hemocytoblasts and RBC precursors
have nuclei. But, as cell division continues toward producing the RBC, a cell called
a normoblast is made. The normoblast continues to manufacture
hemoglobin (at this point, it looks like a normal cell, but somewhat red).
Then, the normoblast ejects its nucleus. The cytoplasm continues to make hemoglobin,
even without a nucleus, because the instructions from the nucleus are still in the
cytoplasm, even though the nucleus is gone. Eventually, enough hemoglobin is made
and the cell is released into the blood as an RBC.
The odd-looking shape of the RBC actually allows lots of surface
area to exist on this cell. That is another important feature of the RBC because it
helps there be more room on the RBC for gas exchange across its membrane. The RBCs
are rather small, averaging about 8 mm in diameter; a small
size also helps them increase their surface area.
Life of RBC: Red blood cells can't last forever. They have no nucleus. They have to squeeze through the teeniest of blood vessels all day long! The
odds are against them-- either they will run out of materials they need because they have
no nucleus to make more, or they will squeeze through one too many teeny blood vessels and
burst. They can only last so long.
On average, a red blood cell will survive 120 days
(that's about 4 months... which is pretty good, considering their difficulties). Over
120 days, each RBC wll travel through the entire body about 75,000 times! Wow!
Regulation of RBC production: Some people have a hard time with the change
in altitude for a couple of days. That's because at higher elevations there is less
oxygen in the air... so to get enough oxygen, we actually need more RBCs in our body.
A drop in oxygen levels in one's body triggers the release of
erythropoietin. Erythropoietin is released from the kidneys
and liver, and it triggers erythropoiesis to occur. Within a couple days, new RBCs
are in the blood, and a person's RBC level increase.
Just like with the other hormones, there is a negative
feedback loop to control erythropoiesis. As oxygen levels return to normal, the
kidneys (and liver) stop making erythropoietin. The extra RBC production declines as
long as oxygen levels remain normal.
Why RBCs are enucleated: Because they were descended from ancestors that had evolved red blood
cells that had the ability to enucleate themselves as part of the
process of red blood cell maturation. That's about it. This is useful
because:
1. The enucleated red blood cell has more room for carrying hemoglobin and thus oxygen if it's not carrying around a nucleus
2. The enucleated red blood cell doesn't need an aerobic metabolism to
support a nucleus, and therefore isn't itself using up the oxygen that
it's carrying
3. The enucleated red blood cell is more bendy than a nucleated one,
and can thus fit through narrower capillaries, which is more efficient
since more of the body mass can be given over to cells of the body
rather than capillary volume.
Enucleation less understood: Prior to entering the blood stream, developing erythroid or red blood
cells condense and expel their nucleus. This unusual process occurs
millions of times per minute in a healthy adult, and is unique to
mammals. However, our understanding of this process is very limited.
Mammalian erythrocytes or red blood cells circulate without a nucleus.
During development in the bone marrow, erythroid progenitors expand,
mature and condense and expel their nucleus. This is estimated to occur 2
millions/second in a healthy adult human. The processes that regulate
this event are extremely poorly defined. Interestingly, enucleation is
restricted to mammals. All mammals possess enucleated red blood cells
whereas erythrocytes of birds, reptiles, amphibians and fish all possess
their nuclei. We are very interested in exploring the processes by
which mammalian erythroid cells condense and expel their nuclei and
asking why other vertebrates do not.
Enucleation is the hallmark of erythropoiesis in mammals. Previously, we
determined that yolk sac–derived primitive erythroblasts mature in the
bloodstream and enucleate between embryonic day (E)14.5 and E16.5 of
mouse gestation. While definitive erythroblasts enucleate by nuclear
extrusion, generating reticulocytes and small, nucleated cells with a
thin rim of cytoplasm (“pyrenocytes”), it is unclear by what mechanism
primitive erythroblasts enucleate. Immunohistochemical examination of
fetal blood revealed primitive pyrenocytes that were confirmed by
multispectral imaging flow cytometry to constitute a distinct, transient
cell population. The frequency of primitive erythroblasts was higher in
the liver than the bloodstream, suggesting that they enucleate in the
liver, a possibility supported by their proximity to liver macrophages
and the isolation of erythroblast islands containing primitive
erythroblasts. Furthermore, primitive erythroblasts can reconstitute
erythroblast islands in vitro by attaching to fetal liver–derived
macrophages, an association mediated in part by α4 integrin. Late-stage
primitive erythroblasts fail to enucleate in vitro unless cocultured
with macrophage cells. Our studies indicate that primitive erythroblasts
enucleate by nuclear extrusion to generate erythrocytes and pyrenocytes
and suggest this occurs in the fetal liver in association with
macrophages. Continued studies comparing primitive and definitive
erythropoiesis will lead to an improved understanding of terminal
erythroid maturation.
Human erythrocytes are produced through a process named erythropoiesis, developing from committed stem cells
to mature erythrocytes in about 7 days. When matured, these cells live
in blood circulation for about 100 to 120 days (and 80 to 90 days in a
full term infant). At the end of their lifespan, they become senescent, and are removed from circulation.
Erythropoiesis
is the development process by which new erythrocytes are produced; it
lasts about 7 days. Through this process erythrocytes are continuously
produced in the red bone marrow of large bones, at a rate of about 2
million per second in a healthy adult. (In the embryo, the liver is the
main site of red blood cell production.) The production can be
stimulated by the hormone
erythropoietin (EPO), synthesised by the kidney. Just before and after
leaving the bone marrow, the developing cells are known as
reticulocytes; these comprise about 1% of circulating red blood cells.
Blood in a dish: in vitro synthesis of red blood cells
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| In vitro production of RBCs: the 2-step erythroid culture system |
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