Chemotactic factors for neutrophils

Leukotrienes increase capillary permeability and serve as chemotactic factors for neutrophil granulocytes. As "slow-reacting substances of anaphylaxis," they are involved in allergic reactions (p. 326) together with PG, they evoke the spectrum of characteristic inflammatory symptoms redness, heat, swelling, and pain. 

Histamine, platelet-activating factor, leukotrienes (C4, D4, E4), prostaglandin D2, neutral proteases Histamine, platelet-activating factor, leukotrienes, prostaglandin Cytokines (chemokines and TNE), leukotriene B4, chemotactic factors for neutrophils and eosinophils... 

Hermanowitz, A., Kossman, S. (1984). Neutrophil function and infectious disease occupationally exposed to phosphoorganic pesticides role of mononuclear-derived chemotactic factor for neutrophils. Clin. Immunol. Immunopathol. 33 13. 

Based on the fact that interleukin-1 (IF-1) induces migration of leukocytes to sites of injection, IF-1 was thought to have chemotactic activity. In fact, leukocyte-derived chemoattractants for phagocytic cells were present in partially purified preparations of IF-1 (Fuger et al, 1983 Sauder et al, 1984). However, when purified to homogeneity, IF-1 lost its chemotactic activity. Further studies revealed that the partially purified IF-1 preparations were contaminated with both a chemotactic factor for monocytes and a monocyte-derived neutrophil chemotactic factor, termed MDNCF (Yoshimura et al, 1987, 1989 Matsushima et al, 1988, 1989). These paradoxical observations were resolved by data showing that IF-1 was a potent inducer of these chemotactic factors. The same mononuclear cell-derived neutrophil attrac-tants were also identified by several other laboratories of (Schroder et al, 1987 Walz et al, 1987). Eater, Farsen et al (1989) reported that MDNCF was chemotactic for T lymphocytes as well as neutrophils, and, based on the presumed involvement of MDNCF in the immune response, it was renamed IF-8 (Farsen et al, 1989 Oppenheim et al, 1991). 

Chemotactic factor for primed eosinophils, basophils, and neutrophils... 

Figure 4.8. Hypothesis for the local generation of mast-cell-stimulating peptides by the action of neutrophil-derived enzymes on albumin. Initial stimulation of the mast cell by any of a variety of agents causes the release of preformed histamine (H) neutrophil and eosinophil chemotactic factors (NCF, ECF) and enzymes and the de novo synthesis of prostaglandins (PG) and leukotrienes (LT). These agents increase vascular permeability and vessel diameter. As a result, albumin and later neutrophils (PMN) enter the tissue space where the latter undergo phagocytosis and the secretion of proteolytic enzymes to the extracellular space where they act on albumin to generate NRP (neurotensin-related peptide) and HRP (histamine-releasing peptide). These newly formed peptides then act as a second stimulus to the mast cell. In addition NRP and HRP may affect other immunocompetent celt such as monocytes, macrophages or eosinophils.

One approach to examining inflammation is the assay reported by Elgebaly et al. (1987) for the release of chemotactic factors. Earlier work has elegantly shown that neutrophil or macrophage infiltration from either the endothelial or epithelial surface... 

C5a is inactivated by the myeloperoxidase-H202 system, which oxidises a methionine residue (Met 70) on the molecule group A streptococcal endo-proteinases also abolish chemotactic activity of C5a and related compounds. Neutrophil lysosomal enzymes (e.g. elastase and cathepsin G) also destroy C5a chemotactic activity, but as these proteases are inhibited by the serum antiproteinases, a -antiproteinase and a2-macroglobulin, the physiological role of neutrophilic proteases in the inactivation of C5a is questionable. Two chemotactic factor inactivators have been found in human serum an a-globulin that specifically and irreversibly inactivates C5-derived chemotactic factors, and a / -globulin that inactivates bacterial chemotactic factors. These activities are heat labile (destroyed by treatment at 56 °C for 30 min) and are distinct from those attributable to anaphylatoxin inactivator. An apparently specific inhibitor of C5-derived chemotactic activity has also been described in human synovial fluid and peritoneal fluid. This factor (molecular mass of 40 kDa) is heat stable and acts directly on C5a. 

Colchicine, an alkaloid obtained from the autumn crocus, has long been used and is relatively selective for the treatment of acute gouty arthritis. Unlike many of the newer agents for use in gout, colchicine has minimal effects on uric acid synthesis and excretion it decreases inflammation associated with this disorder. It is thought that colchicine somehow prevents the release of the chemotactic factors and/or inflammatory cytokines from the neutrophils, and this in turn decreases the attraction of more neutrophils into the affected area (Fig. 37.1).The ability of colchicine to bind to leukocyte microtubules in a reversible covalent complex and cause their depolymerization also may be a factor in decreasing the attraction of the motile leukocytes into the inflamed area. 

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