Inflammatory cell distribution in guinea pig airways and its relationship to airway reactivity Fiona Westerhof 1,CA , Wim Timens 2 , Annemiek van Oosten 2 , Annet B. Zuidhof 1 , Nathalie Nauta 2 , Martin Schuiling 1 , Johannes T. W. M. Vos 2 , Johan Zaagsma 1 , Herman Meurs 1 and Wilko Coers 2 1 Department of Molecular Pharmacology, University Centre for Pharmacy, A. Deusinglaan 1, 9713 AV Groningen, the Netherlands; 2 Department of Pathology and Laboratory Medicine, University Hospital Groningen, Hanzeplein 1, 9713 GZ Groningen, the Netherlands CA Corresponding Author Tel: (+)31 50 3633 304 Fax: (+)31 50 3636 908 E-mail: F.J.Westerhof@farm.rug.nl ALTHOUGH airway inflammation and airway hyper- reactivity are observed after allergen inhalation both in allergic humans and animals, little is known about the mechanisms by which inflammatory cells can contribute to allergen-induced airway hyperreactiv- ity. To understand how inflammatory cell infiltration can contribute to airway hyperreactivity, the location of these cells within the airways may be crucial. Using a guinea pig model of acute allergic asthma, we investigated the inflammatory cell infiltration in different airway compartments at 6 and 24 h (i.e. after the early and the late asthmatic reaction, respec- tively) after allergen or saline challenge in relation to changes in airway reactivity (AR) to histamine. At 6 h after allergen challenge, a threefold (p < 0.01) increase in the AR to histamine was observed. At 24 h after challenge, the AR to histamine was lower, but still significantly enhanced (1.6-fold, p < 0.05). Adventitial eosinophil and neutrophil numbers in both bronchi and bronchioli were significantly increased at 6 h post-allergen provocation as com- pared with saline (p < 0.01 for all), while there was a strong tendency to enhanced eosinophils in the bronchial submucosa at this time point (p = 0.08). At 24 h after allergen challenge, the eosinophilic and neutrophilic cell infiltration was reduced. CD3 + T lymphocytes were increased in the adventitial com- partment of the large airways (p < 0.05) and in the parenchyma (p < 0.05) at 24 h post-allergen, while numbers of CD8 + cells did not differ from saline treatment at any time point post-provocation. The results indicate that, after allergen provoca- tion, inflammatory cell numbers in the airways are mainly elevated in the adventitial compartment. The adventitial inflammation could be important for the development of allergen-induced airway hyperreactivity. Key words: Eosinophils, Neutrophils, Lymphocytes, Sub- mucosa, Adventitia, Parenchyma, Allergen-challenge, Airway hyperreactivity, Guinea pigs Introduction Allergic asthma in man is clinically characterized by bronchoconstriction in response to inhaled aero- allergens, resulting in an early asthmatic reaction (EAR) that is often followed by a late asthmatic reaction (LAR). The EAR is thought to be primarily caused by an immunoglobulin (Ig)E-mediated release of mast cell mediators, while the LAR is associated with the recruitment and activation of inflammatory cells in the lung, including eosinophils, neutrophils and lymphocytes. 1–4 Another important feature of allergic asthma is the development of increased reactivity of the airways to non-specific stimuli following allergen exposure, referred to as airway hyperreactivity (AHR). Allergen- induced AHR has been observed in patients with a dual asthmatic reaction, and may already be present before the onset of the LAR. 5–8 It is generally thought that inflammatory cell influx in the airways is involved in the development of AHR. However, a close relationship between the number of inflammatory cells in the airway lumen or mucosa and chronic AHR has not invariably been found, which may possibly be due to airway remodeling after prolonged inflammation. 9–11 Although information from biopsy studies is avail- able about inflammation in the airway wall of asthmatics, little is known about the distribution of inflammatory cells throughout the entire airway circumference and lung tissue of these patients. Detailed knowledge about this distribution may be ISSN 0962-9351 print/ISSN 1466-1861 online/01/030143-12 © 2001 Taylor & Francis Ltd 143 DOI: 10.1080/09629350120072716 Research Paper Mediators of Inflammation, 10, 143–154 (2001)