Leukocyte degranulation

Recently, the activities of host defense peptides related to the resolution of infection have been suggested to result in part from nondirect antimicrobial activities. It has been postulated that immunomodulation may represent the primary action of these peptides in vivo as the immunomodulatory activities are retained under physiological conditions in contrast to the direct antimicrobial activities of most natural mammalian host defense peptides. These immunomodulatory activities include, but are not limited to, direct chemotactic activity, induction of chemokines and other immune mediators, stimulation of leukocyte degranulation and other microbicidal activities, effects on leukocyte and epithelial cell survival and apoptosis, stimulation of epithelial and endothelial cell proliferation, promotion of wound healing and angiogenesis, antiendotoxic and anti-inflammatory activities, and adjuvant fiinctions. These will be described in detail in the following sections and a summary is found in Table 1. 

Topham MK, Carveth HJ, McIntyre TM, Prescott SM, Zimmerman GA Human endothelial cells regulate polymorphonuclear leukocyte degranulation. FASEB J 1998 12 733-746. 

Mansfield, P.J., Hinkovska-Galcheva, V., Carey, S.S., Shayman, J.A. and Boxer, L.A. (2002). Regulation of polymorphonudear leukocyte degranulation and oxidant production by ceramide through inhibition of phospholipase D. Blood 99, 1434-1441. 

CC, and one CX3C and XC chemokine receptors have been cloned so far [2]. Receptor binding initiates a cascade of intracellular events mediated by the receptor-associated heterotrimeric G-proteins. These G-protein subunits trigger various effector enzymes that lead to the activation not only of chemotaxis but also to a wide range of fimctions in different leukocytes such as an increase in the respiratory burst, degranulation, phagocytosis, and lipid mediator synthesis. 

Bhattacharyya, S.P., Drucker, I., Reshef, T., Kirshenbaum, A.S., Metcalfe, D.D. and Mekori, Y.A. (1998) Activated T lymphocytes induce degranulation and cytokine production by human mast cells following cell-to-cell contact. Journal of Leukocyte Biology 63, 337-341. 

Inamura, N., Mekori, Y.A., Bhattacharyya, S.P., Bianchine, P.J. and Metcalfe, D.D. (1998) Induction and enhancement of FcERI-dependent mast cell degranulation following coculture with activated T cells dependency on ICAM-1- and leukocyte function-associated antigen (LFA)-l-mediated heterotypic aggregation. Journal of Immunology 160, 4026-4033. 

Pfizer s tenidap (CP-66,248) (157), another enolic compound, was also more potent (500-fold) toward CO over 5-LO inhibition in human ISN (0.032 /iM and 18 /iM, respectively) [379-381]. Efficacy in rheumatoid arthritis clinical trials has been reported [380,382] in patients, serum levels of acute phase proteins and synovial fluid levels of IL-1 were reduced by tenidap, in contrast to the lack of this effect with NSAIDs. Besides CO/5-LO inhibition, a variety of in vitro activities have been reported, including a number of effects on monocyte functions and differentiation [379], inhibition of neutrophil degranulation [382], inhibition of the activation of neutrophil collagenase [383], inhibition of leukocyte-endothelial cell adhesion [384], and inhibition of LTB4-induced neutrophil chemotaxis [385]. Al-... 

Kimura Y, Okuda H, Kubo M. 1995 Effects of stilbenes isolated from medicinal plants on arachidonate metabolism and degranulation in human polymorphonuclear leukocytes. J Ethnopharmacol 45 131-139. 

Of their many preformed intracellular mediators, histamine, not only plays an important physiological role, but can be used as a marker for these cells. In the human peripheral blood, the basophil is the only leukocyte that contains histamine. As a result, histamine release from human blood leukocyte preparations can be used to monitor basophil degranulation. In this chapter we will describe the histamine release assay, alternative techniques to measure the concentration of histamine and, finally, a method to purify human basophils to confirm that the chemokines are acting directly on the basophil. 

Acid staining leukocyte associated with allergic inflammation. See Lee, J.J. and Lee, N.A, Eosinophil degranulation an evolutionary vestige or a universally destructive effector function, Clin. Exp. Allergy 35, 986-994, 2005. 

Cromoglicate inhibits mast-ceU degranulation and histamine release induced by phosphohpase A2, but does not interfere with the interaction of antigen and reaginic antibodies. Evidence is accumulating that it has an important stabilizing action on leukocytes, apart from mast cells, such as neutrophils, eosinophils, and monocytes, and that it also affects nerve reflexes in the lung (2). 

Additional biological tests have been suggested to improve the accuracy further. The leukocyte histamine release test has been found helpful (75) but it is expensive and time-consuming. Several surface molecules have been studied as markers, for example CD63. IgE-mediated degranulation of basophils after incubation of the patient s serum with a neuromuscular blocking agent can... 

Effects of Natural Products Isolated from Medicinal Plants on Arachidonate Metabolism and Degranulation in Platelets and Leukocytes. 

Human and animal studies evidenced that polymorphonuclear (PMN) leukocytes are involved in the development of CHD, angina, and in a number of pathophysiological conditions related to chronic inflanunation and vascular injury. Leukotriens released by PMN under the challenge of various stimuli, promote chemotaxis, aggregation and degranulation of... 

Klein, L.M., Lavker, R.M., Matis, W.L. and Murphy, G.F. (1989). Degranulation of human mast cells induces an endothelial antigen central to leukocyte adhesion. Proc. Natl. Acad. Sci. USA 86, 8972-8976. 

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