Substance P stimulates the loss of cell-associated high molecular weight glycoconjugates from cultured hamster tracheal epithelial cells through polymorphonuclear leucocytes activation.
Abnormal and excessive mucus secretion is a characteristic feature of many chronic inflammatory lung diseases accompanied by the influx of polymorphonuclear leucocytes (PMNs) into the airway and the release of substance P from the peripheral endings of primary sensory neurons. We examined whether PMNs activated by substance P (10 microM) can affect the secretion of high-molecular-weight glycoconjugates (HMWG), which is used as a marker of mucus, from cultured hamster tracheal epithelial cells. We measured both the released and the cell-associated HMWG. Substance P-activated PMNs (10(6) cells/ml) reduced the amount of cell-associated HMWG to 76% of the control level, but did not affect the amount of the released HMWG. The reduction of the amount of cell-associated HMWG was inhibited by ONO-5046, a specific elastase inhibitor. In addition, the HMWG was digested by the activated PMNs. These findings suggested that substance P stimulates the loss of the cell-associated HMWG and degrades the released HMWG from cultured hamster tracheal epithelial cells through PMNs activation.
Yoshitake
K
K
Department of Pharmacological Sciences, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Isohama
Y
Y
Kai
H
H
Takahama
K
K
Miyata
T
T
D000818:Animals; D002478:Cells, Cultured; D006224:Cricetinae; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006001:Glycoconjugates / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D008970:Molecular Weight; D009092:Mucous Membrane / Q000378:metabolism; D018375:Neutrophil Activation / Q000502:physiology*; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology; D014132:Trachea / Q000166:cytology / Q000378:metabolism*
D006001:Glycoconjugates; D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; D013373:Substance P; C069195:sivelestat; D010196:Pancreatic Elastase; D005998:Glycine