SUBSTANCE-P INCREASES NEUTROPHIL ADHESION TO BRONCHIAL EPITHELIAL-CELLS

Polymorphonuclear neutrophils (PMNs) accumulate within the airways dur ing acute and chronic bronchitis and can adhere to bronchial epitheliu m. Substance P (SP), a neuropeptide released from the primary afferent nerve endings, has been shown to have a proinflammatory effect on PMN s. To test the hypothesis that SP could modulate PMN bronchial epithel ial cell adherence, bovine bronchial epithelial cells (BBECs) were iso lated and cultured, and the capacity of SP to modulate PMN-BBEC adhere nce was evaluated. SP interacted with BBECs to induce an increase in P MN adhesion (14.7 +/- 1.2% vs 5.3 +/- 0.7% adherence, p < 0.01). The e ffect of SP was both time- and dose-dependent with maximal responses a t 6 h and 10(-10) M. The effect was reproduced by the carboxyl-termina l sequence of the molecule (SP 6-11). Importantly, pretreatment of the BBECs with the tachykinin SP receptor (NK1) antagonist, CP-96,345, si gnificantly reduced the increase in adhesion induced by SP (p < 0.01). Furthermore, treatment of the BBECs with antibodies against CD11 a (L FA-1), CD11b (MAC-1), or ICAM-1 significantly decreased SP-induced adh erence (p < 0.01 all comparisons). Conversely, SP stimulation of PMN i nduced a dose-dependent, rapid (within 5 min) increase in adherence. T his effect was also mediated by the carboxy end of the molecule and wa s decreased by CP-96,345, again suggesting that this effect was NK1 me diated. These data demonstrate the SP has the capacity for modulating PMN-BBEC interactions and suggest an important role for SP in modulati ng airway inflammation.