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In
hematology Hematology (American and British English spelling differences#ae and oe, spelled haematology in British English) is the branch of medicine concerned with the study of the cause, prognosis, treatment, and prevention of diseases related to bloo ...
, reticulocytes are immature
red blood cell Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood cel ...
s (RBCs). In the process of
erythropoiesis Erythropoiesis (from Greek ''erythro'', meaning ''red'' and ''poiesis'', meaning ''to make'') is the process which produces red blood cells (erythrocytes), which is the development from erythropoietic stem cell to mature red blood cell. It is s ...
(red blood cell formation), reticulocytes develop and mature in the
bone marrow Bone marrow is a semi-solid biological tissue, tissue found within the Spongy bone, spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It i ...
and then circulate for about a day in the blood stream before developing into mature red blood cells. Like mature red blood cells, in
mammals A mammal () is a vertebrate animal of the class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three middle e ...
, reticulocytes do not have a
cell nucleus The cell nucleus (; : nuclei) is a membrane-bound organelle found in eukaryote, eukaryotic cell (biology), cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, have #Anucleated_cells, ...
. They are called reticulocytes because of a reticular (mesh-like) network of
ribosomal RNA Ribosomal ribonucleic acid (rRNA) is a type of non-coding RNA which is the primary component of ribosomes, essential to all cells. rRNA is a ribozyme which carries out protein synthesis in ribosomes. Ribosomal RNA is transcribed from ribosomal ...
that becomes visible under a microscope with certain stains such as new methylene blue and
Romanowsky stain Romanowsky staining is a prototypical staining technique that was the forerunner of several distinct but similar stains widely used in hematology (the study of blood) and cytopathology (the study of diseased cells). Romanowsky-type stains are use ...
.


Clinical significance

To accurately measure reticulocyte counts, automated counters use a combination of laser excitation, detectors and a
fluorescent dye A fluorophore (or fluorochrome, similarly to a chromophore) is a fluorescence, fluorescent chemical compound that can re-emit light upon light excitation. Fluorophores typically contain several combined aromaticity, aromatic groups, or planar o ...
that marks
RNA Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...
and
DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...
(such as titan yellow or polymethine). Reticulocytes appear slightly bluer than other red cells when looked at with the normal
Romanowsky stain Romanowsky staining is a prototypical staining technique that was the forerunner of several distinct but similar stains widely used in hematology (the study of blood) and cytopathology (the study of diseased cells). Romanowsky-type stains are use ...
. Reticulocytes are also relatively large, a characteristic that is described by the
mean corpuscular volume The mean corpuscular volume, or mean cell volume (MCV), is a measure of the average volume of a red blood corpuscle (or red blood cell). The measure is obtained by multiplying a volume of blood by the proportion of blood that is cellular (the hem ...
. The normal fraction of reticulocytes in the blood depends on the clinical situation but is usually 0.5% to 2.5% in adults and 2% to 6% in infants. A reticulocyte percentage that is higher than "normal" can be a sign of
anemia Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...
, but this depends on the health of a person's bone marrow. Calculating the reticulocyte production index is an important step in understanding whether or not the reticulocyte count is appropriate to the situation. This is often a more important question than whether the percentage is in the normal range; for instance, if someone is anemic but has a reticulocyte percentage of only 1%, the bone marrow is likely not producing new blood cells at a rate that will correct the anemia.


Immature reticulocyte fraction (IRF)

Reticulocytes at less mature levels can be detected by having higher intensity fluorescence regions. An increased immature reticulocyte fraction (IRF), specifically an IRF more than or equal to 0.23, together with an increased absolute reticulocyte count, generally indicates an adequate erythroid response to anemia. An IRF of more than 0.23 but a subnormal or normal absolute reticulocyte count (with a corresponding reticulocyte production index of less than or equal to 2) is seen in for example acute infection, iron deficiency anemia, human immunodeficiency virus infection, sickle disease with crisis, pregnancy, and myelodysplastic syndrome. An IRF of less than 0.23 is seen in diseases that lead to decreased erythropoietic activity, predominantly chronic renal insufficiency.


Development

The development begins with the expulsion of the normoblast nucleus, and is followed by loss of organelles and remodeling of the plasma membrane, giving rise to an
erythrocyte Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood ce ...
.


Research

Reticulocytes are a valuable tool for biologists who study
protein translation In biology, translation is the process in living cells in which proteins are produced using RNA molecules as templates. The generated protein is a sequence of amino acids. This sequence is determined by the sequence of nucleotides in the RNA. T ...
. Reticulocytes are unusual among cells in that they contain all of the machinery necessary to translate proteins but lack a nucleus. Since a cell's nucleus contains many components that make studying translation difficult, these cells are quite useful. Scientists can collect reticulocytes from animals such as rabbits and extract the
mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...
and translation enzymes to study protein translation in a cell-free,
in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...
system, allowing greater control over the environment in which proteins are being synthesized.


References

{{Authority control Blood cells Human cells