title: The IL-5 receptor on human bronchus selectively primes for hyperresponsiveness.
abstract: BACKGROUND
  The role of IL-5-induced eosinophilia in airway hyperresponsiveness has been questioned. In addition, eosinophil-independent IL-5-induced airway hyperresponsiveness has been demonstrated in animals.
  
  
  OBJECTIVE
  In this study, IL-5 was investigated for direct effects on human bronchial responsiveness.
  
  
  METHODS
  Human muscle preparations were isolated from organ donor and surgical tissue. Bronchus, jejunum, and saphenous vein were incubated for 24 hours in vitro with recombinant human (rh) IL-5. Contractility to acetylcholine (bronchus, jejunum) and phenylephrine (saphenous vein) was then investigated. RT-PCR was used to evaluate IL-5 receptor alpha (IL-5R(alpha)) expression in various tissues and to assess bronchus and saphenous vein eosinophils through use of CCR3 expression.
  
  
  RESULTS
  rhIL-5 primed bronchus for an exaggerated contraction to acetylcholine. The acetylcholine concentration that produced 50% of the control maximum response was reduced 17- to 20-fold in bronchus treated with 1 and 10 nmol/L rhIL-5. The lower concentration of 0.1 nmol/L rhIL-5 had no effect. The rhIL-5 effect on bronchial contractility was attenuated by antibodies to IL-5 (TRFK-5; 100 nmol/L) and human IL-5R(alpha) (100 nmol/L). rhIL-5 (10 nmol/L) did not enhance contractility of saphenous vein or jejunum. When RT-PCR was used, IL-5R(alpha) expression was strong in bronchus muscle, weak in trachealis, saphenous vein, and atrial muscle, and undetectable in jejunum, urinary bladder, and pulmonary and renal artery muscle. Comparable weak expression of CCR3 was identified in bronchus and saphenous vein.
  
  
  CONCLUSIONS
  The findings are consistent with an airway tissue-selective expression of the IL-5 receptor that mediates IL-5-induced airway hyperresponsiveness independent of eosinophils. In asthma, in which IL-5 expression is elevated, IL-5 might directly induce bronchial hyperresponsiveness.
authors.affiliation: Allergy, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Rizzo
authors.forename: Richard
authors.initials: R
authors.lastname: Yang
authors.forename: Scott
authors.initials: S
authors.lastname: Greenfeder
authors.forename: Robert W
authors.initials: RW
authors.lastname: Egan
authors.forename: Romain A
authors.initials: RA
authors.lastname: Pauwels
authors.forename: John A
authors.initials: JA
authors.lastname: Hey
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001980:Bronchi / Q000276:immunology* / Q000502:physiology; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D016084:Bronchoconstriction; D005260:Female; D006801:Humans; D015848:Interleukin-5 / Q000235:genetics / Q000494:pharmacology*; D007583:Jejunum / Q000187:drug effects / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism*; D053649:Receptors, Interleukin-5; D011994:Recombinant Proteins / Q000494:pharmacology; D012501:Saphenous Vein / Q000187:drug effects / Q000502:physiology
chemical_list: C515350:CCR3 protein, human; D015848:Interleukin-5; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5; D011994:Recombinant Proteins; D010656:Phenylephrine; D000109:Acetylcholine