Pulmonary immune cells in health and disease: the eosinophil leucocyte (Part II)

Abstract

The second part of this review on eosinophils focuses on biological cell functions and surveys the various deleterious mechanisms involved in the eosinophil-dominated inflammatory reaction. It discusses the possible pathogenic role of eosinophils in several eosinophil-related diseases, such as parasitic infections, interstitial lung disorders and bronchial diseases, graft rejection, vasculitic granulomatous disorders, pleural effusion, and bronchogenic tumours.The final section of the article highlights the possible recent pharmacological and future therapeutic approaches in modifying eosinophil recruitment and function. Eur Respir J., 1994, 7, 743-760 This paper is published as a follow-on to "Pulmonary immune cells in health and disease: the eosinophil leucocyte (Part I)"* (Eur Respir J, 1994; 7: 519-543). Biological cell functionsThe eosinophil mediates its effector functions through various distinct cellular mechanisms, namely nonoxidative, oxidative, and humoral mechanisms ( fig. 7). Nonoxidative mechanismsAs mentioned previously, the three basic proteins as well as eosinophil peroxidase (EPO) have toxic properties independent of molecular oxygen species. For instance, major basic protein (MBP) [323], eosinophil cationic protein (ECP) [324] and EPO in the presence of hydrogen superoxide and a halide [99] kill helminthic parasites in vitro. In addition, these proteins are toxic for tumour cells and/or mammalian cells [325], including human pulmonary parenchyma and interstitial matrix [326,327], cultured human lung epithelial cells [328], and guinea-pig respiratory epithelium [252, 253,329]. Furthermore, it has been demonstrated that MBP damages human bronchial epithelium, which consists of desquamation and destruction of ciliated cells [329]. Finally, release of their granule proteins by plateletactivating factor (PAF)-activated intact eosinophils has been shown to imitate the characteristic pathological findings of airway epithelium in asthma [330].In addition to their cytotoxic action, eosinophil cationic proteins at certain subtoxic concentrations also stimulate other inflammatory cells. For instance, MBP and ECP have been shown to degranulate platelets [305], induce histamine release from mast cells and basophils [240, 245,331], as well as superoxide anion generation and lysosomal enzyme release by human neutrophils [264].Finally, eosinophil proteins may affect airway muscle function and hyperresponsiveness. Recent reports investigating the effects of direct intratracheal instillation of purified eosinophil granule proteins on pulmonary function and airway responsiveness in primates [281,332] have shown that MBP induces a dose-related increase in airway responsiveness to inhaled methacholine. In the same model, both MBP and EPO caused a transient bronchoconstriction immediately after instillation, that resolved within 1 h. Interestingly, other eosinophil granular proteins failed to effect airway responsiveness or pulmonary function.Mode of action. The mode of action of these basic proteins is n...

CD8 T Cells Modulate CD4 T-Cell and Eosinophil-Mediated Pulmonary Pathology in Pneumocystis Pneumonia in B-Cell-Deficient Mice

“…Not only did these mice have abundant eosinophils in the alveolar space, there was also greater activation and degranulation of the eosinophils, as indicated by higher levels of EPO in the BALF. Eosinophil granule proteins such as EPO and MBP are known to be cytotoxic in vitro, 21 and there is also some evidence for their involvement in pulmonary pathology in vivo (although at least in asthma models, there are clear differences in this respect between mice and humans 24,25 ). 17,22,23 The possible effector mechanisms in MT mice in which only CD8 T cells were present are not as clear.…”

Tryptase Activates the Mitogen-Activated Protein Kinase/Activator Protein-1 Pathway in Human Peripheral Blood Eosinophils, Causing Cytokine Production and Release

“…In this study we have further investigated the influence of mast cells on eosinophil activation by assessing whether mast cells could induce IL-6 and IL-8 production and release from eosinophils. Both these proinflammatory cytokines are produced by eosinophils in vitro (16,17) and participate in the allergic inflammatory responses (15,20,21).…”

“…Two cytokines with proinflammatory properties, IL-6 and IL-8, are produced by eosinophils (16,17). IL-8 is a potent granulocyte chemoattractant and can serve as a marker of tissue eosinophilia (18,19).…”

“…The first-strand cDNA synthesis reaction was catalyzed by SuperScript II RNase H Ϫ Reverse Transcriptase and oligo(dT) [12][13][14][15][16][17][18] primer (Life Technologies, Rockville, MD) according to the manufacturer's instructions. The generated complementary DNA was amplified using 1.25 U of Taq DNA polymerase and dNTP mixture and IL-8 (5Ј-ATGACTTCCAAGCTGGCCGTGGCT and 3Ј-TCTCAGCCCTCTTC AAAAACTTCTC) primers (Clontech Laboratories, Palo Alto, CA) in the presence of 10% glycerol (Sigma-Aldrich) as a specificity enhancer.…”

C/EBP regulates the promoter of the eosinophil-derived neurotoxin/RNS2 gene in human eosinophilic cells

“…Eosinophils play an important role in protection against parasites and are also involved in the pathogenesis of allergic diseases, such as allergic asthma and atopic dermatitis [1,2]. Parasite killing and tissue damage found in allergic lesions are both linked to production of toxic oxygen metabolites and to the release of eosinophil granule proteins by degranulation or exocytosis [2][3][4].…”