Gap-junctional coupling between neutrophils and endothelial cells: a novel modulator of transendothelial migration.
Communication between leukocytes and endothelial cells is crucial for inflammatory reactions. Paracrine cross-talk and outside-in signaling (via adhesion molecules) have been characterized as communication pathways to date. As leukocytes and endothelial cells express connexins, we considered intercellular communication via gap junctions an intriguing additional concept. We found that gap-junctional coupling between neutrophils and endothelium occurred in a time-dependent, bidirectional manner and was facilitated by adhesion. After blockade of connexins, transmigration of neutrophils through the endothelial layer was enhanced, and the barrier function of cell monolayers was reduced during transmigration. Tumor necrosis factor alpha decreased coupling. In the presence of connexins, transmigration of neutrophils did not alter permeability. Thus, neutrophils couple to endothelium via gap junctions, functionally modulating transmigration and leakiness. Gap-junctional coupling may be a novel way of leukocyte-endothelial communication.
Zahler
Stefan
S
Institute of Physiology, Ludwig-Maximilians University, Schillerstrasse 44, 80336 Munich, Germany. s.zahler@lrz.uni-muenchen.de
Hoffmann
Anke
A
Gloe
Torsten
T
Pohl
Ulrich
U
D002199:Capillary Permeability / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000502:physiology*; D002465:Cell Movement; D002634:Chemotaxis, Leukocyte; D017630:Connexins / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology*; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D009504:Neutrophils / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology
D017630:Connexins; D014409:Tumor Necrosis Factor-alpha