Increased cAMP levels in stimulated neutrophils inhibit their adhesion to human bronchial epithelial cells

Am J Physiol. 1997 Apr;272(4 Pt 1):L580-7. doi: 10.1152/ajplung.1997.272.4.L580.


Bronchial epithelial cells express the intercellular adhesion molecule-1 that mediates binding of activated neutrophils via interaction with Mac-1 and/or leukocyte function-associated antigen-1. In this study, we examined whether increased intracellular levels of adenosine 3',5'-cyclic monophosphate (cAMP) affected neutrophil adhesion to the human bronchial epithelial cells. It was found that the N-formylmethionyl-leucyl-phenylalanine (fMLP)-stimulated neutrophil adhesion was concentration dependently inhibited when the cAMP analogs dibutyryl adenosine 3',5'-cyclic monophosphate or 8-bromoadenosine 3',5'-cyclic monophosphate were present. The beta-adrenergic receptor agonists isoprenaline and salmeterol, in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX), were also able to inhibit the fMLP-stimulated adhesion of neutrophils to bronchial epithelial cells. These agonists in combination with IBMX significantly increased the intracellular cAMP level in both neutrophils and epithelial cells. Preincubation of neutrophils with the long-acting beta2-adrenergic receptor agonist salmeterol (in the presence of IBMX) inhibited their fMLP-stimulated adhesion to epithelial cells, whereas pretreatment of epithelial cells did not influence the adhesion process. When ethanol-fixed epithelium was used, salmeterol pretreatment also diminished the adhesion of stimulated neutrophils. Moreover, combinations of salmeterol or isoprenaline with IBMX inhibited fMLP-upregulated Mac-1 expression. Therefore, we conclude from these data that elevation of intracellular cAMP in the neutrophil inhibits stimulated neutrophil adhesion to bronchial epithelial cells via Mac-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
  • Adenylyl Cyclases / metabolism
  • Adrenergic beta-Agonists / pharmacology
  • Albuterol / analogs & derivatives
  • Albuterol / pharmacology
  • Bronchi / cytology*
  • Bronchi / metabolism
  • Bucladesine / pharmacology
  • Cell Adhesion / drug effects
  • Cell Line
  • Cells, Cultured
  • Cyclic AMP / blood*
  • Cyclic AMP / metabolism
  • Enzyme Activation
  • Epithelial Cells
  • Epithelium / metabolism
  • Humans
  • Macrophage-1 Antigen / metabolism
  • Neutrophils / drug effects
  • Neutrophils / metabolism*
  • Neutrophils / physiology*
  • Receptors, Adrenergic, beta / metabolism
  • Salmeterol Xinafoate


  • Adrenergic beta-Agonists
  • Macrophage-1 Antigen
  • Receptors, Adrenergic, beta
  • 8-Bromo Cyclic Adenosine Monophosphate
  • Bucladesine
  • Salmeterol Xinafoate
  • Cyclic AMP
  • Adenylyl Cyclases
  • Albuterol