Neutrophils 68

Neutrophils and host defence The fight against infection 

These polymorphs are divided into three subgroups by virtue of the staining properties of their cytoplasmic contents when treated with dye mixtures. Thus, eosinophils stain with acid dyes such as eosin and appear red in stained blood films, basophils stain with basic dyes and appear blue whilst neutrophils stain with both types of dye and their cytoplasm appears purple. The differences between the cytoplasmic contents in these cells types is much more fundamental than is suggested by these simple staining properties. The granules of basophils, neutrophils and eosinophils contain distinct molecular constituents that confer upon the cells their specialised functions during infection and inflammation. 

The full name of these cells is neutrophilic polymorphonuclear leukocytes, but the terms neutrophil and, less-commonly now, polymorph are generally used to describe this cell (Fig. 1.1a). In fact, most preparations of neutrophils contain about 95-97% neutrophils, the remainder being largely eosinophils, because the commonly-used separation techniques do not efficiently separate these cell types. Neutrophils are the most abundant white cell in the blood, accounting for 40-65% of white blood cells, and are found at concentrations usually in the range 3-5 x 106 cells/ml blood. This number can increase dramatically (up to tenfold) in cases of infection. They have a relatively short half-life in the circulation (estimated at about 8-20 h), but this may be extended to up to several days if the cells leave the circulation and enter tissues - although it is difficult to measure the lifespan of a tissue neutrophil. Because of the large numbers of neutrophils in the circulation and their relatively short lifespan, vast numbers of neutrophils enter and 

After the binding of the pathogen to the neutrophil surface via these receptors, the neutrophil must respond by activating its bactericidal arsenal. This activation is achieved through the occupancy of receptors, which trig- 

By analogy with T lymphocytes, the migration of neutrophils from the peripheral circulation into mucosal surfoces has been conceptualized as consisting of three separate steps (Butcher, 1991). 

Selectins mediate the initial weak tethering of neutrophils to the endothelial wall. This results in characteristic rolling of the neutrophils along the endothelium under conditions of heightened shear force. L-selectin (LECAM-1) is constitutively expressed on neutrophils (Lasky, 1991), whereas E-selectin (ELAM-1) expression is induced on endothelial cells by exposure to endotoxin, TNFa or 

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White Blood Cells. White blood cells, or leukocytes, have varying function and morphology. Mononuclear leukocytes include lymphocyte B and T-ceUs, monocytes, and progenitor cells. Polynuclear granulocytes include neutrophils, basophils, and eosinophils. The most important groups in cell separation are lymphocytes, monocytes, and granulocytes. 

Fig. 2. Mass density distribution of blood components A, platelets B, monocytes C, lymphocytes D, basophils E, neutrophils F, erythrocytes and G,...

Histamine in the Blood. After its release, histamine diffuses rapidly into the blood stream and surrounding tissues (12). Histamine appears in blood within 2.5 min after its release, peaks at 5 min, and returns to baseline levels by 15 to 30 min. In humans, the diurnal mean of plasma histamine levels is 0.13 ng/g. In urine, elevations of histamine or metaboUtes are more prolonged than plasma elevations. Consequendy, abnormahties are more easily detected by urinary histamine assay. About one-half of the histamine in normal blood is in basophils, one-third in eosinophils, and one-seventh in neutrophils the remainder is distributed among all the other blood components. Increases in blood histamine levels occur in several pathological... 

Platinum—polyethyleneimine complexes prevent the division of bacteria, and are being tested as carriers in the treatment of cancer and vimses (445—447). Encapsulated PEIs containing nucleic acid bases activate the neutrophils in human blood (448). 

Similar results have been reported in sublethaHy and lethaHy irradiated dogs, where G-CSF reduced the severity and duration of neutropenia and the duration of thrombocytopenia (161). G-CSF increases the survival of lethaHy irradiated animals by inducing eadier recovery of neutrophils and platelets. GM-CSF also decreases the severity and duration of neutropenia in dogs exposed to 2.4 Gy (2400 rad) TBI, but does not influence monocyte or lymphocyte recovery (162), indicating its expected selective action. 

TNE- a also protects mice against the lethal effects of radiation (164). TNE- a given before sublethal kradiation reduces the decline of neutrophils and total blood counts and accelerates the recovery of peripheral blood cells (190). TNE- a also alters the radiosensitivity of murine G1 progenitors (191). 

Leukotriene B4, formed by enzymic hydrolysis of LTA4, is chemotactic for macrophages and neutrophils at concentrations as low as 1 ng/ml. The stereochemistry of the conjugated triene subunit was established by synthesis which also made LTB4 available in quantity for biological research. 

Leukotriene B5 can be biosynthesized in the body from eicosapentaenoic acid, which is ingested in the form of dietary fish lipid. Synthetic LTB5 was synthesized as outlined below and found to have only 20% of the neutrophil chemotactic activity of LTB4, a fact which may be relevant to the antiinflammatory effect of dietary marine lipid. 

When exposure is repeated, the allergen binds between two adjacent IgE molecules. This causes release of inflammatory mediators (histamine, leukotrienes, chemotactic factors). These act locally and cause smooth muscle contraction, increased vascular permeability, mucous gland secretion, and infiltration of inflammatory cells (neutrophils and eosinophils). However, histamine can also be released by non-IgE-mediated mechanisms (e.g., due to exposure to certain fungi). 463... 

Campbell, A. K., Patel, A. K., Razavi, Z. S., and McCapra, F. (1988). Formation of the calcium-activated photoprotein obelin from apo-obelin and mRNA inside human neutrophils. Biochem. J. 252 143-149. 

Colepicolo, P., et al. (1990). A sensitive and specific assay for superoxide anion released by neutrophils or macrophages based on bioluminescence of polynoidin. Anal. Biochem. 184 369-374. 

Lucas, M., and Solano, F. (1992). Coelenterazine is a superoxide anion-sensitive chemiluminescent probe its usefulness in the assay of respiratory burst in neutrophils. Anal. Biochem. 206 273-277. 

Roberts, P. A., Knight, J., and Campbell, A. K. (1987). Pholasin — a biolu-minescent indicator for detecting activation of single neutrophils. Anal. Biochem. 160 139-148. 

Further neutrophil influx and amplification of inflammation and tissue injury... 

Frequently, the EAR is followed by a late phase response 4-6 h later and it is caused by the pulmonary sequestration of eosinophils, neutrophils, mast cells, and T-lymphocytes. This leukocyte recruitment depends on mast cell-derived mediators such as TNFa and various chemokines, as well as on the expression of adhesion molecules on leukocytes (e.g. VLA-4, CD11/18) and vascular endothelial cells (e.g. VCAM-1, ICAM-1, E-selectin). Products of these leukocytes have several functions First, they cause the second phase of bron-choconstriction, mucus secretion, and airway swelling second, they cause tissue destruction third, they launch and entertain the chronic inflammation. 

Bronchial Asthma. Figure 2 Mechanisms of bronchial hyperresponsiveness. Toxic products from eosinophils [cationic peptides, reactive oxygen species (ROS)] cause epithelial injury. Nerve endings become easily accessible to mediators from mast cells, eosinophils [eosinophil-derived neurotoxin (EDN)], and neutrophils, and to airborne toxicants such as S02. Activation of nerve endings stimulates effector cells like mucosal glands and airway smooth muscle either directly or by cholinergic reflexes. 

Basic (pH) proteins directed against pathogens. Examples are the major basic protein from mast cells, the eosinophilic cationic proteins from eosinophils, and defensins from epithelial cells and neutrophilic granulocytes. 

Chemotaxis is the detection of and coordinated movement toward a chemical compound by a cell or organism, e.g., neutrophils move towards an area of infection because of chemicals released by infected tissues. 

COPD is a chronic inflammatory disease that results from prolonged and repeated inhalation of particles and gases, chronic (or latent) infection or an interaction of these factors. In many cases, the inflammation persists even when the exposure (in most cases smoking) is stopped. Prominent among the infiltrating leukocytes are neutrophils, CD8+ lymphocytes (Co-receptor for the T-cell receptor. CD8+ is specific for the class IMHC protein. It is expressed on the surface of cytotoxic T-cells and natural killer cells.) and CD68+ monocytic cells (A lysosomal antigen. All cells that rich in... 

One intensively investigated feature of the inflammatory process in COPD is the release of proteases from neutrophils and monocytic cells that destroy elastin and other components of the interstitial matrix (Table 1). The best studied protease is neutrophil elastase. Independent of its elastolytic activity, neutrophil elastase is a potent secretagogue. More recently matrix metalloproteases (MMP) have received increasing attention, in particular MMP 12 (macrophages elastase). To which extent and how exactly these proteases become activated is not clear at present. 

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