Induction of hyperresponsiveness in human airway tissue by neutrophils: mechanism of action

S. Z. Anticevich, J. M. Hughes, J. L. Black, C. L. Armour

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39 Citations (Scopus)


Background The two main features of asthma are bronchial hyperresponsiveness and inflammation. The inflammatory response in asthma consists of infiltration and activation of a variety of inflammatory cells including neutrophils. Our previous studies have shown that stimulated neutrophil supernatants cause hyperresponsiveness of human bronchial tissue in vitro.

Objective To investigate the effect of the sensitization status of the tissue and the albumin concentration used to prepare supernatants on the response of human bronchial tissue to stimulated neutrophil supernatants.

Methods Neutrophil supernatants were prepared from human isolated blood in the presence of varying concentrations of albumin (0%, 0.1% and 4%), Neutrophil supernatants were added to sensitized and non-sensitized human isolated bronchial tissue which was stimulated with electrical field stimulation (EFS) (20 s every 4min). Receptor antagonists specific for the prostaglandin and thromboxane (10−7M GR3219I), platelet activating factor (10−6M WEB 2086), leukotriene D4 (10−6M MK-679) and neurokinin A (10−7M SR48968) receptors were used to identify neutrophil products responsible for the effects observed in the bronchial tissue. Results In non-sensitized human bronchial tissue, stimulated neutrophil supernatants induced a direct contraction in the presence of 0% and 0.1 % but not 4% albumin. This contraction was due to leukotriene D4 as MK-679 completely inhibited the contraction. In contrast, stimulated neutrophil supernatants increased responsiveness of sensitized human bronchial tissue to EFS. The increased responsiveness was observed only in the presence of 0.1% albumin, with the site of modulation likely to be prejunctional on the parasympathetic nerve. The increased responsiveness was not inhibited by any of the antagonists tested.

Conclusion Sensitization status of the tissue and albumin concentration effect the responsiveness of human bronchial tissue to stimulated neutrophil supernatant. Our results suggest a possible role for neutrophils in hyperresponsiveness.
Original languageEnglish
Pages (from-to)549-556
Number of pages8
JournalClinical and Experimental Allergy
Issue number5
Publication statusPublished - 1996
Externally publishedYes


  • neutrophils
  • albumin
  • sensitization
  • human airways
  • hyperresponsiveness
  • contraction
  • antagonists


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