Mast cells and cell-to-cell interactions in airways.
Dog mastocytomas (anatomic and biochemical features comparable to normal dog and human mast cells) were used to study actions of mast cell mediators on several airway effector systems. We showed mastocytoma cell adherence to both cultured tracheal epithelial cells and tracheal tissue sections for greater than 48 h that was abolished completely by pretreatment of mast cells with proteases. This mast cell-epithelial cell adhesion-interaction reaction is probably mediated by a mast cell plasma membrane protein. Mast cell mediators stimulate short circuit current and ion flux across dog tracheal epithelia mounted in Ussing chambers. Pretreatment of epithelia with indomethacin blocks this effect, probably by inhibiting LTC4-induced activation of epithelial cyclooxygenases. Mastocytoma cells also increase secretion from cultured serous submucosal gland cells. Blockade of cyclooxygenase and lipoxygenase pathways in mastocytoma cells activated by calcium ionophore does not alter secretion of the serous cells induced by mastocytoma supernatant, but secretion induced by mastocytoma supernatant or purified mast cell chymase is markedly reduced by an inhibitor of chymase. These results suggest that mast cells can alter airway secretions not only by actions on ion flux in epithelial cells but also by actions on submucosal gland secretion; this latter action appears to be mediated by mast cell chymase. Finally, supernatants from mastocytoma cells stimulated by calcium ionophore greatly increase the sensitivity and magnitude of the contractile response of dog bronchial smooth muscle to histamine. These effects are blocked by an inhibitor of mast cell tryptase.(ABSTRACT TRUNCATED AT 250 WORDS)
Gold
W M
WM
Cardiovascular Research Institute, University of California, San Francisco 94143-0130.
Lazarus
S C
SC
D000818:Animals; D002450:Cell Communication; D002460:Cell Line; D004285:Dogs; D004848:Epithelium / Q000502:physiology; D066298:In Vitro Techniques; D008407:Mast Cells / Q000502:physiology*; D012515:Mast-Cell Sarcoma; D014132:Trachea / Q000166:cytology*