Granulocyte neutrophile

Neutrophil granulocytes are highly specialized, short-lived (lifetime in the bloodstream 5 days, at the site of inflammation 2 days), non-dividing white blood cells. As professional phagocytes, they represent a central pillar of the innate immune system and play a decisive role in antibacterial and antifugal immune defence.

Neutrophil granulocytes are called "neutrophil" because they do not stain strongly with basic or eosin dyes, i.e. they are "neutral". Other leukocyte species are called "basophilic"(basophilic granulocytes) or "eosinophilic"(eosinophil granulocytes) because of their staining behaviour.

The term "polymorphonuclear leukocytes (PMN)" is also common because the nucleus of the cells is segmented in many ways. Hypersegmented nuclei (nuclei divided into more than 5 segments) in neutrophilic granulocytes are more common in vitamin B12 or folic acid deficiency (most common cause alcoholism). Left-shifting is the proliferation of immature precursors of granulocytes (rod nuclei, metamyelocytes, myelocytes, promyelocytes). A left shift is usually an expression of an acute inflammatory reaction of the organism.

Mature cell segment-nucleated PMNs make up the majority of circulating neutrophil granulocytes. Rod-nucleated (rod-like nucleus: standard value up to 4%) PMNs are young neutrophil granulocytes. They can occur more frequently in acute inflammation (left shift).

Similar to macrophages, neutrophil granulocytes can occur in 3 functional stages: dormant, primed and activated. Activated neutrophil granulocytes show the strongest antimicrobial and cytotoxic activity.

Like all leukocytes in the bone marrow, PMNs are formed from pluripotent haematopoietic stem cells. The growth factor G-CSF (Granulocyte Colony Stimulating Factor) is of essential importance here. After maturing in the bone marrow, the PMNs are released into the blood stream. There they circulate for a few days.

Neutrophil granulocytes contain various granulae. These granulae are responsible for the destruction of phagocytized antigens within the phagolyyssomes. They are also released into the extracellular space, causing necrosis. The environment is protected by plasma proteins such as alpha2-macroglobuin and alpha1-antitrypsin. The granulae of neutrophil ganulocytes are divided into 3 classes:

• primary or azurophilic granules (containing: cathepsin G, myeloperoxidase, neutrophil elastases, proteases ). They are mainly responsible for the destruction of microorganisms and their phagocytosis.
• specific (secondary) granules (lactoferrin), lysozyme, collagenase, phospholipase A2, CR3, CR4, laminin receptors, etc.
• tertiary granules (small storage granules)(gelatinase - matrix metalloproteinase), cathepsin B and D, plasminogen activator, alpha-mannosidase...

Neutrophil granulocytes are the first cells to migrate from the bloodstream at a site of inflammation. Pus consists mainly of neutrophil granulocytes. In detail, the neutrophil infiltration of an inflammation site is initiated by the expression of different adhesion molecules (E and P selectins) on the luminal side of vessels of inflamed areas. P-selectin is stored in the alpha-granules of platelets and in the female-palatal corpuscles of endothelial cells. After activation, P-selectin reaches the surface of thrombocytes and endothelial cells. As a result, PMNs no longer circulate freely but roll slowly along the inner vessel wall. The PMNs activated in this way express integrins, adhesion molecules that anchor them firmly to the vessel wall. By following chemotactic signals from the inflamed tissue (e.g. Interleukin-8 or TNF-alpha), they pass through the vessel wall (extravasation) and infiltrate the perivascular tissue. At the site of the inflammation, different types of tissue are injected. Effector functions of the PMNs are activated at the site of inflammation. These include:

• Phagocytosis: PMNs are phagocytes which are activated by pattern recognition receptors (PRR)
• Granule exocytosis: Neutrophil granulocytes have an important function in the non-specific defence by their ability to phagocytose. After opsonisation of a foreign organism, it is absorbed into the phagocytic vacuole and usually destroyed immediately. During this process, lysosomes fuse with the phagocytic vacuole. Reactive oxygen compounds(ROS) are released during this process.
• Netosis: A further important function of neutrophil granulocytes is the formation of so-called NETs (acronym for Neutrophil Extracellular Traps), net-like DNA structures that are formed during cell death of the granulocytes. In this filigree DNA network, various microorganisms can be trapped and killed. This special type of cell death is called netosis. It differs clearly from the process of apoptosis solely by the acuteity of the process (NETs occur within 10 min. ).
• Oxidative burst: This process releases a large amount of oxygen radicals which destroy microbial or oncological pathogens. Normal cells are also always damaged.
• Cytokine and chemokine release: PMNs can release a large number of pro-inflammatory molecules which activate other immune cells.

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