Eosinophil degranulation

Kita H, Abu-Ghazaleh RI, Sanderson CJ, Gleich GJ Effect of steroids on iimnimoglobulin-induced eosinophil degranulation. J Allergy Clin Immunol 1991 87 70-77. 

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. 

Pathologic studies have demonstrated a perivascular, lymphocytic infiltrate with eosinophils in the dermis, fascia, and skeletal muscle, with variable numbers of eosinophils. The perivascular infiltrate was accompanied by thickening of the capillary and arteriolar endothelium in dermal, fascial, and muscle vessels. The frequent occurrence of microangiopathy (disease of the small blood vessels) in biopsy specimens suggests that ischemia (deficiency of blood supply) may contribute to tissue injury. Deposition of major basic protein (an eosinophil-specific protein) in affected tissue of some patients suggests that cytotoxic eosinophil degranulation products may also play a role in the pathogenesis of EMS. 

Peripheral blood eosinophiha is almost always present in ICEP when blood count is performed prior to corticosteroid treatment (systemic corticosteroids may decrease dramatically the eosinophil cell count within 24—48 horn s), with a mean blood eosinophilia over 5 x 10 eosinophils/L in most series. Alveolar eosinophilia usually greater than 40% at BAL differential cell count is a hallmark of ICEP (9,60), with a mean of about 60% at differential cell count (9), and is key to the diagnosis. Total blood IgE level is increased in about half the cases. C-reactive protein is elevated. Urine excretion of the EDN/eosinophil protein X (EPX) is markedly increased, indicating active eosinophil degranulation (61). 

Cottin V, DeviUer P, Tardy F, et al. Urinary eosinophil-derived neurotoxin/protein X a simple method for assessing eosinophil degranulation in vivo. J Allergy Clin Immunol 1998 101 116 123. 

This mediator, apart from aggregating platelets and stimulating many cells types, is a very potent mediator in allergic reactions causing bronchoconstriction with a 1,000 times more potency than histamine. It is able to increase vascular permeability and cause chemotaxis and degranulation of eosinophils and neutrophils [14-16]. 

Th2 lymphocytes are one of the primary factors initiating and perpetuating the inflammatory response.7 In addition, proinflammatory mediators such as the leukotrienes generated during mast cell degranulation can increase vascular permeability, leading to airway edema and increased mucus production.8 Eosinophilic infiltration of the airways is a hallmark of asthma, and activated eosinophils can cause bronchoconstriction and AHR.9... 

Figure 4 Stabilized bromine antimicrobials are produced by eosinophils, a type of mammalian white blood cell. Bacteria are captured by phagocytosis and contained intracellularly within vesicles called phagosomes. Granules release cationic surfactants, lytic enzymes, and eosinophil peroxidase into the phagosome in a process known as degranulation. Eosinophil peroxidase, an enzyme that is structurally similar to the bromoperoxidases found in seaweed (Figure I), selectively catalyzes oxidation of bromide to hypobromite by reducing hydrogen peroxide to water. The hypobromite immediately reacts with nitrogenous stabilizers such as aminoethanesulfonic acid (taurine) to form more effective and less toxic antimicrobial agents.

Kampen GT, Stafford S, Adachi T, et al. Eotaxin induces degranulation and che-motaxis of eosinophils through the activation of ERK2 and p38 mitogen-activated protein kinases. Blood 2000 95(6) 1911-1917. 

Mast cell degranulation in response to allergens results in release of mediators such as histamine eosinophil, and neutrophil chemotactic factors leukotrienes C4, D4, and E4 prostaglandins and platelet-activating factor (PAF). Histamine is capable of inducing smooth muscle constriction and bronchospasm and may play a role in mucosal edema and mucus secretion. 

Histamine Release. Histamine release is mainly caused by cross-linking of immunoglobulin E on the mast cell surface by antigens. Basophil degranulation is caused mainly by histamine-releasing factors produced by inflammatory cells, such as neutrophils, platelets, and eosinophils. After its release, histamine diffuses rapidly into the blood stream and surrounding tissues. 

This ligand has a lower affinity for adenosine A, and A2B receptors with pK values <6. A potent inhibitory effects on the generation of reactive oxygen species from human neutrophils and eosinophils and on the degranulation of human granulocytes subsequent to treatment with compound 30 have been described. This findings provide a useful tool for the understanding of the involvement of A2a and A3 ARs in inflammation processes. 

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