Editorial What Is the Role of the Eosinophil?
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161 Thorax 1990;45:161-3 THORAX Thorax: first published as 10.1136/thx.45.3.161 on 1 March 1990. Downloaded from Editorial What is the role of the eosinophil? The eosinophil granulocyte was first described in blood in Eosinophil cationic protein Eosinophil cationic protein 1879 by the German scientist Paul Ehrlich. During the is a heterogeneous but single chained protein with a following decades study of the eosinophil attracted many molecular weight that ranges from 18 to 21 kD. The investigators, who showed among other things that high primary amino acid sequence ofeosinophil cationic protein eosinophil counts in blood were associated with diseases shows substantial homology with eosinophil protein X, such as asthma and with parasite infestations.' 2 It was even angiogenin, and pancreatic ribonuclease. This last concluded that the massive tissue eosinophilia found in homology suggested that eosinophil cationic protein might patients dying from status asthmaticus pointed to a role for have ribonuclease activity, and this has been confirmed.2 22 the eosinophil in asthma and that understanding the The homology with eosinophil protein X indicated a close mechanisms concerned in the creation of tissue eosino- relation between the two proteins and might explain why philia "... would undoubtedly greatly elucidate the one of the monoclonal antibodies, EG2, produced against pathogenesis of asthma." Despite such statements interest eosinophil cationic protein also reacts with eosinophil -in the eosinophil faded and few publications contributing protein X.2" Besides being a weak ribonuclease eosinophil to our understanding of this cell emerged during the cationic protein has several other interesting biological following 50 years. One exception was the work suggesting activities. It is cytotoxic, and has the capacity to kill both that the eosinophil has an important role in our defence mammalian and non-mammalian cells (see below and ref against parasites and that it may protect against many ofthe 24). It also has some non-cytotoxic activities, such as the harmful effects of the mast cell in'the allergic reaction." induction of histamine release from mast cells and baso- Interest in the eosinophil has rekindled over the last decade phils,25 stimulation of glycosaminoglycan production by and the eosinophil is now regarded as a potent proinflam- human fibroblasts,26 and inhibition of T lymphocyte matory cell with considerable tissue injuring potential and responses.27 By these means the eosinophil may regulate possibly a causal role in the development ofdiseases such as cell mediated immunological reactions and tissue repair asthma. This change of view followed the identification processes. In addition, eosinophil cationic protein has been and isolation of several highly cytotoxic secretory proteins shown to shorten the plasma coagulation time by mechan- http://thorax.bmj.com/ from the eosinophil,56 the recognition of the hypereosino- isms related to the enhancement of the activity of factor philic syndrome as a separate disease with evidence of XII,28 and also to preactivate plasminogen.' The former tissue injury,7 and the observation in several studies of a finding may account for the great propensity for throm- direct correlation between eosinophil numbers and activity boembolism in patients with the hypereosinophilic syn- on the one hand and the severity of diseases such as asthma drome. on the other."' Eosinophil protein X (eosinophil derived neurotoxin) Eosinophil protein X and eosinophil derived neurotoxin were purified independently718 and have now been shown on September 26, 2021 by guest. Protected copyright. to be identical proteins."' The protein consists ofone amino Eosinophil proteins acid chain with a molecular weight of about 18 kD. It has Morphologically, the human eosinophil is characterised by 600% homology with eosinophil cationic protein and, on the its content of eosin staining granules, some of which basis of recognition by the monoclonal antibody EG2, contain typical crystalloid formations visible by electron shares at least one epitope with eosinophil cationic microscopy. The granules contain four main proteins.56 protein.2' Eosinophil protein X is a potent ribonuclease and The eosinophil cationic protein, eosinophil peroxidase, it also has some cytotoxic capacity. Like eosinophil cationic eosinophil protein X or eosinophil derived neurotoxin, and protein, it is a potent non-cytotoxic inhibitor of T lym- major basic protein. Major basic protein makes up the phocyte proliferation at concentrations similar to those of crystalloid in the granule, whereas the other proteins are eosinophil cationic protein.27 located in the matrix of the granules. A further protein has Eosinophil peroxidase Eosinophil peroxidase is a two been purified from the human eosinophil.21' This protein chained protein with a heavy chain of 52 kD and a light is found mainly in the plasma membrane and forms the chain of 15 kD.'9 It is distinct from the myeloperoxidase of Charcot-Leyden crystals in tissues. neutrophils. Eosinophil peroxidase is a potent peroxidase The major characteristics ofthe four granule proteins are and constitutes a potent cytotoxic mechanism when com- their high isoelectric points; for some this is above pH 11. bined with a halide and H202. In addition, eosinophil Eosinophil cationic protein and major basic protein were peroxidase may degranulate mast cells in a non-cytotoxic the first proteins to be purified but all four were manner."3 subsequently purified both from normal eosinophils and Major basicprotein Major basic protein is a one chained from eosinophils of patients with the hypereosinophilic protein with a molecular weight of 13-8 kD.'2 It is not syndrome or chronic myeloid leukaemia.1'20 The relative unique to the eosinophil, being found in several other cells. content of the four granule proteins varies with the source The major biological function of eosinophil major basic ofeosinophils. In normal eosinophils, however, the content protein is related to its cytotoxic activities, though like of each of the four proteins seems to be fairly similar-that eosinophil cationic protein and eosinophil peroxidase it is, around 10 ug/106 eosinophils. causes degranulation of mast cells.5 162 Editorial Priniing L- 3 IL -5, GM -CSF been found in various body fluids, such as cerebrospinal MOinnncvtp factors fluid, urine, nasal and lung fluids, sputum, and intestinal Aci hiererice fluid, supporting the view that the eosinophil may act as a M icZratio)n cytotoxic cell in man.10 143"51-60 These clinical studies Activation Thorax: first published as 10.1136/thx.45.3.161 on 1 March 1990. Downloaded from Phagocytosis A C3b. IgG. IgA. icqE suggest that the eosinophil, a hitherto neglected cell, is PAF ECAs probably an important participant in various human Oxidatlve burst diseases besides asthma. Sec retioW Preformed com-ponents C ytotoxIc ECP. EPX'EDN The eosinophil in asthma EPO MBP A role for the eosinophil in asthma has been assumed since Ma,st cell mirid hasophil release Components formed the beginning of this century, when blood and lung on activation ModLulationi of irmiuriological and" O radicals LTC. eosinophilia were first observed in asthmatic patients. inflarnmatory cellular reactiorns PAS PGE Their specific role, whether good or bad, has remained Fibroblast activatiorn enigmatic, however. Horn et al found a relation between the extent of blood eosinophilia and severity of asthma as Modulation of coagulation and fibrinolysis measured by lung function.8 Recent studies extended these observations and showed a close relation between the The human eosinophil. IL-interleukin; GM-CSF-granulocyte macrophage-colony stimulatingfactor; C-complement; PAF-platelet reactivity of the airways and the activity and number of activationfactor; ECAs-eosinophil chemotactic activities; ECP- circulating eosinophils. Circulating eosinophil counts and eosinophil cationic protein; EPX/EDN-eosinophil protein XI serum concentrations of eosinophil cationic protein and eosinophil derived neurotoxin; EPO-eosinophil peroxidase; MBP- major basic protein; L T-leukotriene; PG-prostaglandin. eosinophil protein X have shown a positive correlation with the late response after inhalation challenge with allergen, and it has been suggested that measurements of eosinophil In addition to these four proteins the human eosinophil cationic protein or eosinophil protein X might be used to contains several less well characterised substances,57 predict the occurrence of a late asthmatic reaction.6' In including an arylsulphatase, a collagenase, a histaminase, patients with an equivocal late response the concentrations and a phospholipase D. The putative functions of some of of eosinophil cationic protein and eosinophil protein X these enzymes are the neutralisation of mast cell mediators, were higher than those found in patients with no tendency such as the sulphidopeptide leukotrienes, histamine, and to develop a late response. Another study showed a linear platelet activating factor. These activities have formed the correlation between the extent of exercise induced asthma basis for the hypothesis that the primary function of the and serum eosinophil cationic protein concentrations eosinophil is to regulate the activities of the mast cell in the before exercise, suggesting a relation between the activity allergic reaction. of the eosinophil and the airway reactivity. Release ofgranule proteins from human eosinophils may A relation between airway hyperreactivity