The majority of ECP is released after the cell has left the circulation [56] . Several types of inflammatory stimulation have been shown to cause eosinophil degranulation. Interaction with adhesion molecules [57, 58] , stimulation by leukotriene B 4 (LTB 4 ), platelet activating factor (PAF) [59] , interleukin (IL)-5 [60] immunoglobulins and complement factors C5a and C3a [61] all cause ECP release. Upon stimulation of eosinophils small variants of ECP with sizes 16.1 and 16.3 kDa are released [62] . One line of studies have suggested that during Plasma cell line 0.5 ng/mL inhibition of Ig production anti ECP ab [87] B lymphocyte cell line 1 ng/mL inhibition of Ig production [88] Rat Peritoneal Mast Cells 17 45 min 50 percent increased histamine release [92] Human heart Mast cells 4.7 60 sec 10-80 percent increased histamine release PGD 2 synthesis Ca 2+ , temperature [94] Guinea-pig tracheal epithelium 103 6 hr exfoliation of mucosal cells [79] Feline tracheal epithelium 2.5 1 hr release of respiratory conjugates [99] Human trachea 2.5 [99] Human primary epithelial cells 10 6 hr rECP, necrosis [80] Bovine mucus 100 3 fold altered structure [97] Nasal epithelial cells 2.1 ng/mL upregulation of ICAM-1 [100] Human corneal epithelial cells 100 decreased cell viability [98] Epithelial cell line NCI-H292 20 ng/mL 16 hr upregulation of IGF-1 [102] Human fetal lung fibroblast (HFL1) 10 48 hr release of TGF beta, collagen contraction [81] Human fetal lung fibroblast (HFL1) 10 5 hr rECP and naive, migration anti ECPab [107] Human fetal lung fibroblast (HFL1) 10 6 hr 6 fold increased proteoglycan accumulation [108] Potential effects due to high ECP levels in circulation and skin inflammation whole eosinophil granules are released from disrupted cells ( Figure 4B ) and that internal proteins are subsequently released differentially through the process of piece meal degranulation [4] . Several diseases are associated with eosinophils and ECP. Most common are diseases associated with atopy and the T helper lymphocyte type 2 (TH2) phenotype. Cytokines such as IL-5 [63] , or chemokines such as eotaxin are produced in elevated levels and attract elevated numbers of eosinophils to the lumen and bronchi of the lungs in asthma [49] (Figure 4B ), the nasal mucosa in allergic rhinitis [48] ( Figure 3B ) and to the skin in atopic dermatitis [64] . In addition, the gastrointestinal tract and esophagus are infiltrated during conditions such as ulcerative colitis [65] and eosinophil esophagitis [66] . ECP has been measured in disease and the increase in number of activated eosinophils is associated with elevation of serum ECP (sECP) and plasma ECP levels [67] . Anticoagulants such as EDTA attenuate ECP release from eosinophils giving a snapshot of the in situ ECP level in plasma. sECP level on the other hand is often higher than plasma ECP as it's an artificial measure obtained by detection of the protein released during the blood clotting process in the test tube. sECP is thought to reflect the activation state of eosinophils [68] . ECP has also been detected in several other biological fluids such as bronchoalveolar lavage fluid (BALF), sputum, nasal lavage and in mucosa of the intestine [69] . ECP levels in various biological fluids in various diseases are presented in table 1. ECP measurements in allergic asthma have been found useful in monitoring the disease as sputum ECP correlates with forced expiratory flow (FEV) [70] and the need for glucocorticosteroid (GC) therapy while sECP correlate with eosinophil numbers in blood [71] . sECP is also elevated in some but not all cases of TH2 cytokine associated atopic dermatitis [72] eosinophil esophagitis [73] , parasite infection [74] and childhood respiratory syncytial virus (RSV) infection [75] . Raised levels of ECP have also been found in some cases that are not TH2 associated; a group of patients with bacterial infections had elevated sECP [76] , very high levels were found in nasal secretions from patients with bacterial sinusitis [77] and in sputum of a patient with tuberculosis and drug-induced acute respiratory distress syndrome (ARDS) [78] . Malignancies with primary eosinophilia are associated with the highest measurable sECP levels (see HES and malignancy section). Polymorphisms have been shown both to alter expression level and the function of the protein which might complicate the usage of the protein as a biomarker (see polymorphism section). The pathology attributed to eosinophils and ECP has been of both acute character such as defoliation of airway epithelium or activation of other cells [79] [80] [81] and of a chronic type, such as fibrosis in lungs [49] (Figure 5 ). Below we discuss the studies that indicate how ECP release influence other cell types locally ( Figure 6 ).