Neutrophils
(polymorphonuclear leukocytes, PMNs, polys)

The neutrophil, or the heterophil in birds, reptiles and some mammals, is the predominant granulocyte. In many species it is the predominant leukocyte in health. In health, usually only mature neutrophils are released from marrow to circulate in blood. Since mature neutrophils in prototypical human blood have nuclei that are segmented into lobes of condensed chromatin connected by filaments, mature neutrophils are called segmented neutrophils or segs. The mature neutrophils of many animal species do not have a distinct lobe and filament arrangement (they do have constricted nuclei or irregular/knobbly nuclear outlines), nevertheless, they also are called segmented neutrophils. Neutrophils are part of the innate immune system and are the first line of (and are essential for) defense against bacterial pathogens. Neutrophils have a short half-life - they only persist for 10-15 hours once they have been released into peripheral blood.

Normal mature neutrophils of several species are shown at the right. Canine neutrophils have white cytoplasm that contains small pink specific or secondary granules. Feline neutrophils have cytoplasm that is white and lacks visible granules. Equine neutrophils have white or slightly pink cytoplasm with no visible granules. The nuclei of equine neutrophils typically are long, thin and "knobby" with clumps of condensed chromatin projecting from the sides. Ruminant neutrophils have white cytoplasm with small pink granules; these impart an overall pink tint compared to the other species.

Rabbits, birds, amphibians and reptiles have heterophils. In contrast to the inconspicuous granules of neutrophils, granules in heterophils are large and stained deep orange to red. A typical avian heterophil is shown in the page, "Blood Cells by Species".

Left shift
In some animals, immature neutrophils may be seen in peripheral blood. The presence of immature neutrophils in blood is called a left shift. The most common cause of a left shift is inflammation (inflammatory cytokines stimulate both neutrophil production and release of mature and immature forms from the bone marrow), however immature neutrophils can also be released prematurely in bone marrow disorders, such as leukemia or severe marrow injury.

Immature neutrophils are classified based on their stage of maturation. The earliest identifiable neutrophil precursor is a myelocyte, which differentiates into a metamyelocyte, then a band neutrophil, and finally to a mature segmented neutrophil. Only the myelocyte is capable of division - all the more mature stages (metamyelocyte, band, segmented neutrophil) are incapable of division (post-mitotic). The primary criterion for differentiating immature neutrophils from each other is the shape of their nucleus, which starts to indent or constrict as the cell matures. A myelocyte has a round nucleus, a metamyelocyte has an indented or kidney-bean shaped nucleus and a band has a horse-shoe or parallel-sided shaped nucleus (see image below).

stages of neutrophil maturation
This compilation of images is from a cow with severe inflammation secondary to an acute metritis and peritonitis. The cow had a degenerative left shift (more immature than mature neutrophils were counted). These images represent the different stages of neutrophil maturation: A: Mature segmented neutrophil; B: Band neutrophil; C: Neutrophilic metamyelocyte; D: Neutrophilic myelocyte. Note that the immature neutrophils are also demonstrating moderate toxic change - they have cytoplasmic baasophilia and cytoplasmic vacuolation.

When performing a differntial cell count, we classify neutrophils into the "SEGMENTED" category if the nucleus has regions that are distinctly constricted (more than 50% of the width of the nucleus) or has lateral protrusions resulting in irregular nuclear margins. A cell whose nuclear margins are smooth and parallel (or nearly parallel) is a band neutrophil and should be counted as such. More immature stages are classified by their nuclear shape, as described above. Note that cells between these well-defined stages will always be seen in blood. Under these circumstances, the cell in question will be placed in the more mature category, i.e. a cell with nuclear features halfway between a band and a segmented neutrophil will be called a segmented neutrophil. More immature neutrophils can be counted separately as their specific categories or grouped together as "BAND" neutrophils. At Cornell University, all immature neutrophils (band neutrophils, metamyelocytes and myelocytes) are grouped into the "BAND" category of our differential cell count. Using the image above as an example, the cells B through D would be counted as "BANDS" and only cell A would be counted as a "SEGMENTED" neutrophil. However, if we observe stages that are less mature than a band neutrophil (metamyelocyte or myelocyte), we provide this information in the results. The presence of these more immature stages usually indicates more severe inflammation than the presence of band neutrophils alone. Again, the presence of band or more immature neutrophils in blood is called a left shift and usually indicates an inflammatory leukogram. Note that for a left shift, the band neutrophil count must be higher than the established reference interval for that species, but in general, most animals have very few to no band neutrophils normally in the circulation (some healthy dogs can have low numbers of band neutrophils in their blood). A degenerative left shift is the term used when the absolute numbers of band or immature neutrophils are greater than the absolute numbers of mature or segmented neutrophils. A degenerative left shift indicates severe inflammation, which is usually due to bacterial infection.

A common and important morphologic abnormality of neutrophils is so-called "toxic change". This abnormality occurs when neutrophil maturation in the bone marrow is accelerated, usually as a response to inflammatory cytokines. Thus, a left shift and toxic change indicate an inflammatory leukogram and are usually (but not always) seen together.

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