SUBSTANCE-P STIMULATES THE LOSS OF CELL-ASSOCIATED HIGH-MOLECULAR-WEIGHT GLYCOCONJUGATES FROM CULTURED HAMSTER TRACHEAL EPITHELIAL-CELLS THROUGH POLYMORPHONUCLEAR LEUKOCYTES ACTIVATION

Abnormal and excessive mucus secretion is a characteristic feature of many chronic inflammatory lung diseases accompanied by the influx of p olymorphonuclear 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 mu M) can affect t he 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. Sub stance P-activated PMNs (10(6) cells/ml) reduced the amount of cell-as sociated HMWG to 76% of the control level, but did not affect the amou nt of the released HMWG. The reduction of the amount of cell-associate d HMWG was inhibited by ONO-5046, a specific elastase inhibitor. In ad dition, the HMWG was digested by the activated PMNs. These findings su ggested that substance P stimulates the loss of the cell-associated HM WG and degrades the released HMWG from cultured hamster tracheal epith elial cells through PMNs activation.