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.