title: Airway hyperresponsiveness: first eosinophils and then neuropeptides.
abstract: Airway hyperreactivity to bronchoconstrictor mediators is a main characteristic in the majority of asthmatic patients and correlates well with the severity of the disease. The airways of asthmatic patients are characterized by an inflammatory state resulting in activation of lung tissue cells and attraction and infiltration of leukocytes from the blood. The accumulation of eosinophilic leukocytes is a prominent feature of inflammatory reactions that occurs in allergic asthma. The increase in number of eosinophils is important since it correlates in time with an increase in bronchial hyperresponsiveness. Viral respiratory infections can also induce eosinophilia and airway hyperresponsiveness in humans and animals and can worsen asthmatic reactions. This report reviews current opinions on the relationship between inflammation-induced eosinophil accumulation/activation and the development of airway hyperresponsiveness and the possible role for sensory neuropeptides in this process. Firstly, CC chemokines play an important role in allergic airway inflammation and respiratory viral infections leading to eosinophil recruitment. Secondly, it can be concluded that IL5 is involved in the development in airway hyperresponsiveness. IL5 has profound effects on eosinophils as promoter of growth, differentiation and proliferation, chemoattractant, activator and primer. However, it is conceivable that in animal models for allergic asthma besides IL5 other regulatory mediators may be involved in eosinophil migration and activation in the lung, which in turn will lead to airway hyperresponsiveness. Recent data support the possible role of eotaxin and its eosinophil-specific receptor CCR-3 in eosinophil chemotaxis and activation in allergic asthma. Moreover, it is suggested that the development of airway eosinophilia in vivo involves a two-step mechanism, elicited by eotaxin and IL5. The precise mechanism by which eosinophils induce bronchial hyperresponsiveness is at present unknown. Sensory neuropeptides could be important mediators in this process, since it has been demonstrated that airway nerves are surrounded by and infiltrated with eosinophils after antigen challenge. Sensory neuropeptides could be the final, more downstream, common pathway after eosinophil infiltration and activation in inducing airway hyperresponsiveness due to allergen inhalation or respiratory viral infections. In conclusion, in the process of the development of airway hyperresponsiveness observed during viral infections or in allergic asthma, the IL5/eotaxin-induced infiltration and activation of eosinophils in the airways is evident. Following this step, eosinophil-derived inflammatory mediators will induce the release of sensory neuropeptides (possibly NK2-receptor activating tachykinins) which in turn will lead to airway hyperresponsiveness.
authors.affiliation: Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands. A.D.Kraneveld@FAR.RUU.NL
authors.forename: A D
authors.initials: AD
authors.lastname: Kraneveld
authors.forename: G
authors.initials: G
authors.lastname: Folkerts
authors.forename: A J
authors.initials: AJ
authors.lastname: Van Oosterhout
authors.forename: F P
authors.initials: FP
authors.lastname: Nijkamp
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D004802:Eosinophilia / Q000473:pathology; D004804:Eosinophils / Q000276:immunology / Q000473:pathology* / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D015848:Interleukin-5 / Q000502:physiology; D008954:Models, Biological; D009479:Neuropeptides / Q000276:immunology / Q000502:physiology*; D012141:Respiratory Tract Infections / Q000276:immunology / Q000473:pathology / Q000503:physiopathology
chemical_list: C515456:CCL11 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D016207:Cytokines; D015848:Interleukin-5; D009479:Neuropeptides