Granulocytes include neutrophilic, eosinophilic, and basophilic granulocytes. Together with monocytes, they make phagocytic lineage that normally originates in the bone marrow. We know much less about granulocytopoiesis than about erythrocytopoiesis, but we know that there is a negative feedback between the number of granulocytes in the circulation and granulocytic line in the bone marrow.
Neutrophilic granulocytes play important role in inflammation. They move through the capillary endothelium and come to the site of inflamation.
Kinetic studies of neutrophilic granulocytes showed that there are two compartments in the bone marrow: mitotic (proliferative) and postmitotic (the maturation-storage) compartments. The mitotic compartment consists of 3 parts: myeloblastic, promyelocytic, and myelocytic; and the postmitotic one consists of 2 parts: metamyelocytic (mature compartment), and storage (stab and segmented granulocytes). Only stab granulocytes and mainly segmented granulocytes migrate to the peripheral blood. In the peripheral blood 50% of the granulocytes are located in the so-called marginated pool in the blood capillaries. Under the influence of specific factors (for instance, epinephrine, physical efforts) granulocytes move to the peripheral blood, and in this way the number of leukocytes may increase by 50% (this lasts only 10-15 minutes). From the storage compartment granulocytes may be injected into normal subjects without simultaneously increased production of granulocytes in the bone marrow inasmuch as the quantity of mature granulocytes in the storage compartment is 15 times larger than the number of granulocytes in the peripheral blood. It has been proved that, on the occasion of the normal transfer of granulocytes into the peripheral blood, the storage compartment may sustain the normal number of granulocytes in the peripheral blood during 10 days without making use of the proliferative compartment.
Eosinophilic granulocytes are mostly located in tissues, and not in the peripheral blood. They are produced in the bone marrow. Before moving to tissues they remain in the peripheral blood for about 10 hours. Eosinophilia accompanies immune and allergic reactions. Eosinophilic granulocytes have antihistaminic function, so by eliminating histamine they prevent its activities available for producing edema and smooth muscles spasm. They have power of phagocytosis, but in that ability they are far behind neutrophilis. Eosinophilic granulocytes are able to phagocytize antigen-antibody complexes as well as to use their enzymes to demolish foreign proteins. Their role has not yet been completely explained.
Basophilic granulocytes take part in the reactions of early over-sensitive age, having the role of degrading lipids. Basophilic granules contain histamine and heparin. Under the influence of histamine release factors, basophilic granulocytes release histamine responsible for numerous allergic reactions. Immunoglobulin IgE, by its Fc-fragment, binds to specific receptors located on the membranes of basophilic granulocytes, which also provides the stimulus for the release of histamine from basophilic granules. Basophilic granulocytes release all stored heparin during hyperlipemia after food intake, which enables the degradation of triglycerides into fatty acids and glycerol (heparin activates lipoproteinic lipase).
In order to fulfil their protective role, phagocytes must accumulate on the site of inflammation, come in contact with harmful agents, and phagocytize them, dissolving and removing them. Accumulation of granulocytes and monocytes on the inflammatory site is caused by chemotaxis. After binding with the harmful factors the granulocyte takes these factors in its cytoplasm with the help of pinocytosis or phagocytosis. Phagocytized material is separated from the remainder of the cytoplasm with an invagination of the cell membrane. Such a vesicle is called the phagosome. Subsequently, lysosomes of
granulocytes bind to the phagosomes and discharge their hydrolyzing enzymes, killing and dissolving phagocytized material. Even granulocytes collapse after releasing their enzymes and degranulation.
Biochemical processes occurring during phagocytosis and destruction of phagocytized material are very well known today. Increasing in energy during phagocytosis is followed by increased production of H2O2 . H2O2 , together with oxydized iodide tyrosine, destroys the membrane of the microorganism. Increased glycolysis during phagocytosis, needed for the synthesis of ATP, leads up to producing great amounts of NADH that makes necessary H2O2 under the influence of NADH oxydases. The surplus of H2O2 oxidizes reduced glutathione increasing pentose-hexose monophosphate pathway of glycolysis. Lactic acid produced during glycolysis may increase acidity in the cytoplasm of granulocytes and intensify the activity of hydrolyzing enzymes.
Along with hydrolyzing enzymes, some non-enzymatic substances of granulocytes (phagocytin, leukin, cationic proteins, lactopherin) seem to function bactericidally. Among numerous enzymes in lysosomes (lipase, trypsin, amylase, acid and alkaline phosphatase) only lysozyme and myeloperoxidase seem to have bactericidal activity.