Granulocytes - The Merck Veterinary Manual

Granulocytes

Granulocytes consist of neutrophils, eosinophils, and basophils, which are produced in the bone marrow from a common progenitor cell, the myeloblast. The proliferative (mitotic) pool consists of myeloblasts, promyelocytes, and myelocytes, which are ~20% of the marrow myeloid cells. The storage (maturation) pool, comprising 80% of the marrow myeloid cells, consists of metamyelocytes, band neutrophils, and segmented neutrophils that are functionally mature. During maturation, promyelocytes first form primary granules (lysosomes) that later become inapparent. During the myelocyte stage, granulocytes form specific granules that have characteristic staining affinity, eg, basophilic for basophils, eosinophilic for eosinophils, and neutral for neutrophils. These cytoplasmic granules protect the body against microbial and parasitic infections or, if not modulated, may result in tissue damage.

Neutrophils:

In peripheral blood, neutrophils normally are mature (segmented). Neutrophils from bone marrow enter the peripheral bloodstream, remain for a half-life of ~6 hr, and adhere to the endothelium; when needed, they enter tissues to function primarily in phagocytosis and enzymatic killing of bacteria. They do not return to the vascular bed. The maintenance of normal numbers of neutrophils in the peripheral blood depends on regular replacement from the bone marrow. Small numbers of young (band) neutrophils may normally be found in the peripheral blood of some species such as pigs and dogs (and rarely in horses and cattle).

Döhle bodies, equine blood smear

Morphologic changes in neutrophil cytoplasm, including toxic granulation, diffuse cytoplasmic basophilia, cytoplasmic vacuolation, and Döhle bodies, may occur during systemic bacterial infections or severe inflammation and are referred to as toxic changes. Although all circulating WBC are exposed to the same systemic diseases, only neutrophils are evaluated for toxic changes. Toxic change is graded subjectively as mild, moderate, or marked, based on the number of affected neutrophils and the severity of toxic change. Clinical significance is reflected by the type of toxic change and its severity. Toxic granulation is identified by the presence of pink to purple intracytoplasmic granules within neutrophils; these granules represent primary granules of the neutrophil that have retained their staining affinity. Diffuse cytoplasmic basophilia and cytoplasmic vacuolation frequently occur together. The cytoplasmic basophilia is due to persistent ribosomes, and the cytoplasmic vacuolation possibly due to autodigestion of the cell. Döhle bodies appear as pale blue, intracytoplasmic inclusions within neutrophils. Even when present in high numbers, Döhle bodies alone usually indicate a mild toxic change. They also may occur in clinically healthy cats. Bacterial toxins induce the most severe toxic changes. Severe toxic change is indicated when toxic granulation, diffuse cytoplasmic basophilia, or cytoplasmic vacuolation are present in a moderate to high number of the peripheral blood neutrophils. The presence of many severely toxic neutrophils indicates a guarded to poor prognosis. An autosomal recessive condition in Birman cats results in fine intracytoplasmic eosinophilic granules within neutrophils that may be mistaken for toxic granulation; these cats have normal neutrophil function. Metachromatic intracytoplasmic granules may occur in WBC in metabolic storage diseases.

The magnitude of neutrophilia induced by inflammation is a function of the size of the bone marrow storage pool of granulocytes, hyperplasia of the marrow, and rate of WBC migration into the tissues. The storage pool is quite large in dogs and far smaller in cattle; dogs can sometimes have a reactive WBC count of >100×10³/µL, while counts of >30×10³/µL are uncommon in cattle. Neutrophilia, often the cause of leukocytosis, generally characterizes bacterial infections and conditions associated with extensive tissue necrosis, including burns, trauma, extensive surgery, and neoplasia. Extreme leukocytosis (>100,000/µL) may be associated with neoplasms that produce colony-stimulating factors, Hepatozoon canis infections, leukemias, and closed cavity infections. In pyometra and abscesses, the wall of the cavity inhibits the migration of neutrophils into the site of infection but does not impair the release of leukocyte chemotactic substances. The net effect is a high peripheral neutrophil count, which often includes an increased number of band neutrophils (regenerative left shift).

Neutropenia may occur due to margination of neutrophils (pseudoneutropenia), excessive tissue demand or destruction of neutrophils, or reduced or ineffective granulopoiesis. Neutropenia may occur with overwhelming bacterial infections, especially gram-negative septicemia or endotoxemia, in all species. Immune-mediated destruction of neutrophils occurs in animals, and assays have been developed to detect antineutrophil antibodies in horses. Idiosyncratic drug reactions may result in neutropenia or sometimes pancytopenia, eg, sulfonamides, penicillins, cephalosporins, phenylbutazone in dogs, and chloramphenicol in cats. Feline leukemia virus has also been associated with neutropenia.

Eosinophils:

Eosinophils contain enzymes that modulate products of mast cells or basophils released in response to IgE stimulation. For example, histamine released by basophils or mast cells is modulated by histaminase in eosinophils. The cytoplasmic granules of eosinophils contain proteins that are involved in parasite killing. Eosinophilia is induced by substances that promote allergic responses and hypersensitivity (eg, histamine and allied substances) and by IgE. Eosinophils increase in response to parasitic infections, especially those that involve tissue migration, due to the contact of parasite chitin with host tissues. Eosinophilia occurs in ~50% of dogs with dirofilariasis. The severity of eosinophilia produced by fleas depends on both host sensitivity and severity of the infestation. Eosinophilia also may occur with inflammation of the GI, urogenital, or respiratory tracts, or of the skin. Hypereosinophilic syndrome has been reported in cats; diagnosis requires the presence of >1,500 eosinophils/µL for 6 mo, tissue infiltration and organ dysfunction due to eosinophils, and lack of a recognized etiology. Less commonly, peripheral eosinophilia may be associated with neoplasia. Localized eosinophilic tissue lesions do not necessarily produce a peripheral eosinophilia, eg, the eosinophilic granuloma dermatopathies and oral lesions of cats. Usual WBC differential count techniques are not sufficiently sensitive to reliably detect eosinopenia in a single blood count. The absence of eosinophils in repeated hemograms indicates eosinopenia, which is most commonly reported with corticosteroid-induced (stress) leukograms.

Basophils:

Basophils are rare in all common domestic animals. Basophil granules contain histamine, heparin, and sulfated mucopolysaccharides. Although basophils and mast cells have similar functions and enzymatic contents, basophils do not become mast cells and there is no proof of a common precursor cell. Among species, normal peripheral blood basophil numbers vary inversely with the number of tissue mast cells. For example, in dogs, mast cells are numerous in the tissues, and basophils are rare in blood. A peripheral basophilia is uncommon; however, it does occur in some animals with heartworm disease (and other causes of systemic antigenemia) or pathologic lipemias (eg, liver disease, nephrotic syndrome, and hereditary hyperlipoproteinemias). A basopenia is difficult to document and has no diagnostic significance.