Physiology of Leukocytes in Animals

The blood vascular system is conceptually divided into two compartments:

• The marginating pool consists of the microcirculation at the capillary-tissue interface.

• The circulating pool consists of larger vessels. Blood samples obtained by venipuncture are inherently most representative of the circulating pool.

Flow rate, fluid movement into the extravascular space, and selective WBC adhesion to endothelium are factors that can contribute to marked differences in cell concentration in the two pools. Furthermore, these pools are in hemodynamic equilibrium with each other and the extravascular space. Therefore, WBC concentration can change appreciably because of movement of cells and/or fluid from one pool to the other as a result of a change in equilibrium. In most species, WBCs are roughly equally distributed between the two pools. Cats have a greater distribution of leukocytes within the marginating pool.

WBCs in the circulating pool can be increased by certain physiological responses: epinephrine can redistribute WBCs from the marginating pool to the circulating pool, and corticosteroids can inhibit neutrophil endothelial adherence and tissue migration, which adds to the circulating pool.

Granulocytes include neutrophils, eosinophils, and basophils, all of which are produced in the bone marrow from a common progenitor cell (see the figure Bone Marrow Origins of Circulating Blood Cells). Granulopoiesis is the term used to describe production of these cells.

Bone Marrow Origins of Circulating Blood Cells

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A simplified rendition of the origins of granulocyte development in the bone marrow. Development of lymphocytes, erythrocytes, and platelets is also depicted. Dashed lines indicate potential plasticity between precursor cells.

Wood D. Blood Cell Origins. 2026. Created in BioRender and licensed under CC BY 4.0. https://BioRender.com/21mie78

Courtesy of Dr. Darren Wood.

The proliferative (or mitotic) stages of development consist of myeloblasts, promyelocytes, and myelocytes. Promyelocytes have azurophilic primary granules (lysosomes) that become inapparent in later stages. The storage (or maturation) pool consists of metamyelocytes, band neutrophils, and segmented neutrophils that are functionally mature. Specific granules, which define final cell types, are first produced at the myelocyte stage.

Cell types are recognized by characteristic granule-staining affinity (eg, basophilic granules for basophils, eosinophilic granules for eosinophils, and neutral or nonstaining granules for neutrophils). The population of segmented and band neutrophils in the bone marrow can be substantial in some species (particularly dogs) and is referred to as the marrow granulocyte reserve.

Neutrophils

In blood, neutrophils typically are mature (segmented), with occasional more immature band forms. Neutrophils from bone marrow enter the blood, where they remain for an average of 8 hours. They tend to adhere to the microcirculation endothelium and then unidirectionally enter tissues, where they can participate in host defense. (See photomicrograph of neutrophils.)

Neutrophils, blood smear, dog

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Neutrophils in a photomicrograph of a blood smear from a dog. Wright stain; original magnification 100X.

Courtesy of Dr. Darren Wood.

Given the short lifespan of neutrophils in blood, maintenance of blood neutrophil concentration depends on a relatively high, steady delivery from bone marrow. This balance can change dramatically upon either increased tissue demand associated with the development of an inflammatory process or a stem cell injury that decreases the marrow production rate. During initiation of an inflammatory lesion, local mononuclear cell release of specific stimulating factors rapidly stimulates bone marrow to release neutrophil reserve and accelerate granulopoiesis. When the tissue demand is intense, marrow production and release can accelerate dramatically, resulting in a left shift and toxic changes (see quantitative abnormalities).

Eosinophils

Eosinophils function in parasite killing and also contain enzymes that modulate products of mast cells released in response to antigen-IgE receptor mast cell degranulation in allergic disease. For example, histamine released by mast cells is modulated by histaminase in eosinophils. Eosinophilia is primarily induced by allergic inflammatory responses and tissue-invading parasitic infestations. (See eosinophil photomicrograph.)

Eosinophil, blood smear, cat

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Eosinophil in a photomicrograph of a blood smear from a cat. Wright stain; original magnification 100X.

Courtesy of Dr. Darren Wood.

Less commonly, neoplasia (including mast cell tumors and T-cell lymphoma) is associated with paraneoplastic induction of eosinophilia. Localized eosinophilic tissue lesions do not necessarily produce a peripheral eosinophilia (eg, the eosinophilic granuloma dermatopathies and oral lesions of cats). Eosinopenia is a component of corticosteroid-induced (stress) leukograms.

Basophils

Basophils are rare in all common domestic animals. Basophil granules contain histamine, heparin, and sulfated mucopolysaccharides; understanding of their function is limited. As a result, there is no clear interpretation for basophilia. (See basophil photomicrograph.)

Basophil, blood smear, cat

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Basophil in a photomicrograph of a blood smear from a cat. Wright stain; original magnification 100X.

Courtesy of Dr. Darren Wood.

While uncommon, basophilia can accompany eosinophilia, and it is the latter that is interpreted. Although blood basophils and tissue mast cells have similar enzymatic contents, basophils do not become mast cells; they appear to arise from separate bone marrow stem cells.

Monocytes are formed in the bone marrow from monoblasts and then develop to promonocytes before becoming mature monocytes. (See monocyte photomicrograph.)

Monocyte, blood smear, dog

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Monocyte in a photomicrograph of a blood smear from a dog. Wright stain; original magnification 100X.

Courtesy of Dr. Darren Wood.

Monocytes enter the peripheral blood for approximately 24–36 hours and exit into tissues to mature into tissue macrophages. Monocytes and macrophages perform phagocytosis of organisms and cellular debris at sites of inflammation or tissue injury. They can form multinucleated giant cells, particularly in response to foreign bodies or complex organisms that elicit granuloma formation, such as Mycobacterium spp.

Monocytes and macrophages are a major source of colony-stimulating factors and cytokines that regulate inflammatory responses, and subtypes function as antigen-processing cells.

Lymphocytes originate from bone marrow stem cells and mature in the lymph nodes, spleen, and other subepithelial lymphoid tissues. Mature lymphocytes consist of two major subpopulations:

• B cells (for bone marrow or bursa equivalent) are potential precursors of plasma cells that produce antibodies for humoral immunity.

• T cells (for thymus) engage in cellular immunity (eg, histocompatibility and delayed-type hypersensitivity).

Lymphocytes in tissue can return to the vascular system and recirculate. Some lymphocytes are very long-lived compared with other WBC types. (See lymphocyte photomicrograph.)

Lymphocyte, blood smear, dog

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Lymphocyte in a photomicrograph of a blood smear from a dog. Wright stain; original magnification 100X.

Courtesy of Dr. Darren Wood.