Substance P increases neutrophil adhesion to bronchial epithelial cells.
Polymorphonuclear neutrophils (PMNs) accumulate within the airways during acute and chronic bronchitis and can adhere to bronchial epithelium. Substance P (SP), a neuropeptide released from the primary afferent nerve endings, has been shown to have a proinflammatory effect on PMNs. To test the hypothesis that SP could modulate PMN bronchial epithelial cell adherence, bovine bronchial epithelial cells (BBECs) were isolated and cultured, and the capacity of SP to modulate PMN-BBEC adherence was evaluated. SP interacted with BBECs to induce an increase in PMN adhesion (14.7 +/- 1.2% vs 5.3 +/- 0.7% adherence, p < 0.01). The effect of SP was both time- and dose-dependent with maximal responses at 6 h and 10(-10) M. The effect was reproduced by the carboxyl-terminal sequence of the molecule (SP 6-11). Importantly, pretreatment of the BBECs with the tachykinin SP receptor (NK1) antagonist, CP-96,345, significantly reduced the increase in adhesion induced by SP (p < 0.01). Furthermore, treatment of the BBECs with antibodies against CD11a (LFA-1), CD11b (MAC-1), or ICAM-1 significantly decreased SP-induced adherence (p < 0.01 all comparisons). Conversely, SP stimulation of PMN induced a dose-dependent, rapid (within 5 min) increase in adherence. This effect was also mediated by the carboxy end of the molecule and was decreased by CP-96,345, again suggesting that this effect was NK1 mediated. These data demonstrate the SP has the capacity for modulating PMN-BBEC interactions and suggest an important role for SP in modulating airway inflammation.
DeRose
V
V
Research Service, Omaha Department of Veterans Affairs Medical Center, NE 68105.
Robbins
R A
RA
Snider
R M
RM
Spurzem
J R
JR
Thiele
G M
GM
Rennard
S I
SI
Rubinstein
I
I
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology / Q000276:immunology*; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D004848:Epithelium / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D064729:Neurokinin-1 Receptor Antagonists; D009504:Neutrophils / Q000166:cytology*; D010446:Peptide Fragments / Q000494:pharmacology; D012397:Rosette Formation; D013373:Substance P / Q000494:pharmacology*; D013997:Time Factors
D001713:Biphenyl Compounds; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D018799:Intercellular Adhesion Molecule-1; D013373:Substance P; C066892:CP 96345