Granulocytes

Granulocytes: Neutrophils, Eosinophils and Basophils

  • Macrophages comprise granular leukocytes: neutrophils, eosinophils and basophils. These cells originate from hematopoietic stem cells under the signalling of different cytokines and colony-stimulating factors (granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, etc).
  • Neutrophils make 47-72% of total leukocyte count, basophils – 0-1%, eosinophils – 1-5%.

Granulocytes: Neutrophils, Eosinophils and Basophils

Neutrophil Leukocytes

  • Neutrophils are the most active phagocytes maintaining the reactions of innate immunity.
  • They are short-living cells – the average life span of neutrophils is near 7 h.
  • Neutrophils harbour the granules of various types in their cytoplasm, e.g. primary azurophilic, secondary “specific” and tertiary.
  • Primary granules contain a vast number of enzymes. A pivotal enzyme of primary granules is myeloperoxidase – the specific enzyme of neutrophils.
  • Also, they accumulate neutrophil elastase, catepsins, neutral and acid proteases, β-glucuronidase, and other enzymes as well as microbicidal proteins defensins.
  • Secondary granules contain lactoferrin, lysozyme, collagenase (gelatinase), metalloproteinases and the components of NADPH-oxidase – the enzyme generating respiratory burst.
  • Tertiary granules predominantly harbour gelatinase.
  • Neutrophils show instant response to different Exo- and endogenous stimuli, moving directly to inflammation focus. Of the most efficient chemoattractants for neutrophils are IL-8 and anaphylatoxins C3a and C5a.
  • The basic function of neutrophil cells is phagocytosis. After microbial engulfment NADPH-oxidase triggers the respiratory burst pathway. It is activated via granular enzyme release and reactive oxygen species formation (superoxide anion O2, hydroxyl radicals (•OH), singlet oxygen and many others). These substances render strong bactericidal effects.
  • Neutrophil myeloperoxidase actively participates in microbial destruction generating highly reactive hypochlorite (HOCl) from hydrogen peroxide.
  • The process of phagocytosis is followed by intensive production of inflammatory cytokines.
  • After successful elimination of pathogens by phagocytosis activated neutrophils usually undergo apoptosis in order to limit inflammatory reactions. On the contrary, in the case of highly aggressive pathogens, the neutrophil cell can be destroyed resulting in necrosis.
  • In the situations, where the neutrophils can’t cope with the objects of phagocytosis, they may trigger additional microbicidal mechanism known as the production of neutrophil extracellular traps (or NETs).
  • The process of NETs formation (NETosis) includes the controlled release of neutrophil nuclear DNA together with bactericidal enzymes and proteins from granules through the membrane of the leukocyte.
  • NETosis creates the spatial net-like structures full of microbicidal molecules that cover the large areas within the tissues. As a result, pathogenic agents become captured and confined within the NETs and undergo gradual degradation. Thus, NETs prevent microbial invasion and spread. Complete NETosis results in neutrophil death.
  • As the particular antimicrobial action, NETosis is especially efficient, if the neutrophil encounters the pathogens of larger sizes like fungal and protozoan cells, or parasites. Overall, in the reactions of innate immunity NETosis is regarded now as the process demonstrating the comparable efficacy with conventional phagocytosis.
  • Neutrophil cells bear membrane CD16 (FcγRIII), CD32 (FcγRII), and CD64 (FcγRI) markers; receptors to C3b, C5a and C1q complement components, a great number of adhesion molecules from various protein families (selectins, integrins and many others).

Basophil Leukocytes

  • Basophils circulate in the blood carrying large granules that stain in purple-blue by Romanowsky-Giemsa method. Mast cells are the tissue counterparts of basophils. All of these cells are essential participants in immediate allergic reactions.
  • Basophil granules contain histamine, serotonin, leukotrienes, platelet-activating factor (PAF), heparin, different chemoattractants, and many other potent mediators. They are released from activated basophil after its degranulation that is triggered by specific binding of basophil Fcε-receptor to allergen-specific IgE.
  • Basophil mediators affect blood vessels; thus they increase blood flow and accelerate the inflammatory response.

Eosinophil Leukocytes

  • Eosinophils take part in allergic reactions and in anti-parasitic immunity. Their maturation and life cycle are controlled by IL-3 and IL-5. IL-5 activates eosinophil movement towards the places of mast cell concentration within target tissues and organs, thereby promoting eosinophil tissue infiltration.
  • Granules of eosinophils contain various allergic mediators and cytotoxic proteins, predominantly eosinophil major basic protein. It causes the damage of invaded parasites but can provoke bronchial hypersensitivity, affecting respiratory epithelial cells.
  • Eosinophils are shown to develop the cytotoxic activity to different host cells with subsequent tissue damage.
  • Eosinophils express a great variety of surface receptors, e.g. for C3b and C4 complement components, Fc receptors to IgG and IgE, and many others.