Dissociation of airway responsiveness and bronchoalveolar lavage (BAL) cell composition in sensitized guinea–pigs after daily inhalation of ovalbumin

Abstract

The association between inflammatory cell influx, cell activation status and change of airway responsiveness to acetylcholine (ACh) after daily inhalation of ovalbumin (OA) in sensitized guinea-pigs was investigated. Starting 3 weeks after sensitization (OA at 50 mg/kg s.c.+i.p.) guinea-pigs were exposed daily to 2% OA (10 min; under cover of 0.5 mg/kg mepyramine i.p. 15 min before OA) for 2 weeks. Concentration-response curves (CRCs) for inhaled ACh were performed 24 h after the last OA-challenge and 24 h after another single OA-inhalation 1 week later. CRCs for inhaled ACh were neither affected 24 h after the last OA challenge (daily for two weeks) nor 24 h after another OA-inhalation one week later. In contrast, bronchoalveolar lavage (BAL) from repeatedly OA- sensitized/-challenged guinea-pigs immediately after the last CRC showed a significant increase of total cell count by about tenfold and increases in eosinophils by about 20-fold, neutrophils by 30-fold, macrophages by about fivefold and lymphocytes by about tenfold (P < 0.05, multiple Wilcoxon-test). In contrast, markers of cell activation (EPO, MPO) were significantly decreased (P < 0.05). Methylprednisolone almost completely prevented these changes in increased cell numbers and decreased cell activation (vs OA contr., P < 0.05). The lack of increased airway hyperresponsiveness despite a massive inflammatory cell influx suggests other factors controlling airway responsiveness than inflammation.

Mapping physiological G protein-coupled receptor signaling pathways reveals a role for receptor phosphorylation in airway contraction

“…This dissociation between airway inflammation and the degree of airway hyperresponsiveness has been previously reported in various studies, including observations in asthmatic patients (36) as well as in animal models of allergic inflammatory airway disease (34,37,38). Rather, we propose that in the lung, phosphorylation of the M3-mAChR is important in driving key asthmatic features, such as airway hyperresponsiveness, in part, via M3-mAChR phosphorylation and RhoA-dependent signaling.…”

Inhibition of Arginase I Activity by RNA Interference Attenuates IL-13-Induced Airways Hyperresponsiveness

“…Bronchial hyperreactivity in asthmatics can also occur independently of the development of pulmonary inflammation (53)(54)(55)(56). This disassociation of airways inflammation and AHR has been confirmed in animal models of allergen-induced lung disease (57)(58)(59). Eosinophilia and mucus hypersecretion (albeit reduced) are also features of allergic airways inflammation in IL-13 Ϫ/Ϫ mice (60, 61); however, AHR is critically dependent on this cytokine.…”

Airway Hyperresponsiveness in Anaesthetised Guinea‐Pigs 18–24 Hours after Antigen Inhalation Does Not Occur with All Intravenously Administered Spasmogens

“…The same study, however, showed airway hyperresponsiveness when intravenous histamine was used. Similarly, single spasmogen studies have failed to reveal airway hyperresponsiveness to iv histamine at any time up to 72 hr after ovalbumin challenge (Banner et al 1996) or to acetylcholine (Heuer et al 1994). We have found only one other study which examined a wide range of spasmogens (Crowther et al 1997).…”

“…The concept of non-specific airway hyperresponsiveness in guinea-pigs has been questioned by a lack of airway hyperresponsiveness to inhaled acetylcholine (Heuer et al 1994) or histamine (Banner et al 1996) at 24 hr after an antigen challenge. With no more than two spasmogens under study, however, it is difficult to assess to what extent the airway hyperresponsiveness is non-specific.…”