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(Chest. 2003;123:385S.)
© 2003 American College of Chest Physicians

Histamine Decreases E-Cadherin-Based Adhesion To Increase Permeability of Human Airway Epithelium*

Joseph Zabner, MD; Michael C. Winter, PhD; Sandra Shasby; Dana Ries and D. Michael Shasby, MD, FCCP

* From the Division of Pulmonary and Critical Care Medicine, University of Iowa, Iowa City, IA.

Correspondence to: D. Michael Shasby, MD, FCCP, Division of Pulmonary and Critical Care Medicine, University of Iowa, Iowa City, IA 52242

During the immediate airway response following aerosol antigen challenge of sensitized guinea pigs, there is an increase in airway epithelial permeability to large molecules.1 2 This increase in epithelial permeability is reproduced by aerosol challenge with histamine.3 We hypothesized that these effects were mediated by alterations in E-cadherin-based epithelial cell adhesion. When histamine (10-4 to 10-6 mol/L) was applied to the basolateral surface of primary differentiated human airways epithelial cells, it caused an immediate mean (± SD) fall (18.8 ± 6.25%) in transepithelial resistance (TER) that persisted for 3 to 5 min. The H1 receptor antagonist promethazine blocked the change in TER following histamine application. Interestingly, promethazine itself caused a gradual mean increase in TER of 14.9 ± 1.87%.

EVC304 cells are a transformed bladder epithelium cell line that form tight junctions and express N-cadherin but not E-cadherin. Histamine decreased the TER of ECV304 cells that were transfected with and expressed E-cadherin by 30 ± 5%, but histamine did not change the TER of ECV304 cells expressing lac-Z in the same vector. To more precisely localize the effects of histamine to E-cadherin-based adhesion, and to eliminate the potential response of tight junction structures, we examined the adhesion of L cells transfected with the H1 receptor and E-cadherin to a lawn of an E-cadherin-human Fc fusion protein. The extracellular domain of E-cadherin was fused to the Fc domain of human IgG. The fusion molecule bound to protein G-coated plates, orienting the E-cadherin domain away from the surface of the plate. We cloned the human histamine receptor from ECV304 cells and stably transfected L cells (which have no cadherins or claudins) with both the human H1 receptor and E-cadherin. The adhesion of L cells, expressing the histamine receptor and E-cadherin, to the E-cadherin lawn fell by 50% after exposure to histamine. The adhesion of L cells expressing the histamine receptor alone did not change. We conclude that histamine increases airway epithelial cell permeability by decreasing E-cadherin-based epithelial cell adhesion. These changes in permeability may expose subepithelial tissues to agents that alter their proliferation and physiologic state.


   Footnotes
 
Abbreviation: TER = transepithelial resistance


   References
TOP
 References
 

  1. Ranga, V, Powers, MA, Padilla, M, et al (1983) Effect of allergic bronchoconstriction on airways epithelial permeability to large polar solutes in the guinea pig. Am Rev Respir Dis 128,1065-1070[ISI][Medline]
  2. Goto, Y, Uchida, Y, Nomura, A, et al Dislocation of E-cadherin in the airway epithelium during an antigen-induced asthmatic response. Am J Respir Cell Mol Biol 2000;23,712-718[Abstract/Free Full Text]
  3. Boucher, RC, Ranga, V, Pare, PD, et al Effect of histamine and methacholine on guinea pig tracheal permeability to HRP. J Appl Physiol 1978;45,939-948[Abstract/Free Full Text]




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