Mechanisms of Smokeless Tobacco-Induced Oral Mucosa Inflammation: Role of Bradykinin

Xiao Pei Gao, Jamboor K. Vishwanatha, J. Michael Conlon, Christopher O. Olopade, Israel Rubinstein

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The purpose of this study was to determine whether an aqueous extract of smokeless tobacco (moist snuff) increases clearance of macromolecules from postcapillary venules in the in situ oral mucosa and, if so, whether bradykinin mediated this response. Using intravital microscopy, we found that 20-min suffusion of the extract elicited significant concentration-dependent leaky site formation and increase in clearance of FITC-dextran (molecular mass, 70 kDa) from the hamster cheek pouch (p < 0.05). These responses were associated with a significant increase in bradykinin-like immunoreactivity in the suffusate. Smokeless tobacco extract-induced leaky site formation and increase in clearance of FITC-dextran were significantly attenuated by NPC 17647 and Hoe 140 (p < 0.05), two bradykinin B2 receptor antagonists, but not by desArg9,[Leu8]bradykinin, a bradykinin B1 receptor antagonist. Both bradykinin B2 receptor antagonists had no significant effects on adenosine-induced responses. Indomethacin had no significant effects on smokeless tobacco extract-induced responses. Exposure to smokeless tobacco extract was associated with a significant decrease in angiotensin I-converting enzyme activity and a small, but significant, increase in neutral endopeptidase 24.11 activity in the cheek pouch, two peptidases widely distributed in the microcirculation that cleave and inactivate bradykinin (p < 0.05). Overall, these data suggest that smokeless tobacco elicits plasma exudation in the oral mucosa in vivo in a specific fashion, and that this response is mediated by bradykinin.

Original languageEnglish
Pages (from-to)4624-4633
Number of pages10
JournalJournal of Immunology
Volume157
Issue number10
StatePublished - 15 Nov 1996

Fingerprint

Smokeless Tobacco
Mouth Mucosa
Bradykinin
Inflammation
Cheek
Neprilysin
Venules
Peptidyl-Dipeptidase A
Microcirculation
Indomethacin
Cricetinae
Adenosine
Peptide Hydrolases

Cite this

Gao, X. P., Vishwanatha, J. K., Conlon, J. M., Olopade, C. O., & Rubinstein, I. (1996). Mechanisms of Smokeless Tobacco-Induced Oral Mucosa Inflammation: Role of Bradykinin. Journal of Immunology, 157(10), 4624-4633.
Gao, Xiao Pei ; Vishwanatha, Jamboor K. ; Conlon, J. Michael ; Olopade, Christopher O. ; Rubinstein, Israel. / Mechanisms of Smokeless Tobacco-Induced Oral Mucosa Inflammation : Role of Bradykinin. In: Journal of Immunology. 1996 ; Vol. 157, No. 10. pp. 4624-4633.
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Gao, XP, Vishwanatha, JK, Conlon, JM, Olopade, CO & Rubinstein, I 1996, 'Mechanisms of Smokeless Tobacco-Induced Oral Mucosa Inflammation: Role of Bradykinin', Journal of Immunology, vol. 157, no. 10, pp. 4624-4633.

Mechanisms of Smokeless Tobacco-Induced Oral Mucosa Inflammation : Role of Bradykinin. / Gao, Xiao Pei; Vishwanatha, Jamboor K.; Conlon, J. Michael; Olopade, Christopher O.; Rubinstein, Israel.

In: Journal of Immunology, Vol. 157, No. 10, 15.11.1996, p. 4624-4633.

Research output: Contribution to journalArticle

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T1 - Mechanisms of Smokeless Tobacco-Induced Oral Mucosa Inflammation

T2 - Role of Bradykinin

AU - Gao, Xiao Pei

AU - Vishwanatha, Jamboor K.

AU - Conlon, J. Michael

AU - Olopade, Christopher O.

AU - Rubinstein, Israel

PY - 1996/11/15

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N2 - The purpose of this study was to determine whether an aqueous extract of smokeless tobacco (moist snuff) increases clearance of macromolecules from postcapillary venules in the in situ oral mucosa and, if so, whether bradykinin mediated this response. Using intravital microscopy, we found that 20-min suffusion of the extract elicited significant concentration-dependent leaky site formation and increase in clearance of FITC-dextran (molecular mass, 70 kDa) from the hamster cheek pouch (p < 0.05). These responses were associated with a significant increase in bradykinin-like immunoreactivity in the suffusate. Smokeless tobacco extract-induced leaky site formation and increase in clearance of FITC-dextran were significantly attenuated by NPC 17647 and Hoe 140 (p < 0.05), two bradykinin B2 receptor antagonists, but not by desArg9,[Leu8]bradykinin, a bradykinin B1 receptor antagonist. Both bradykinin B2 receptor antagonists had no significant effects on adenosine-induced responses. Indomethacin had no significant effects on smokeless tobacco extract-induced responses. Exposure to smokeless tobacco extract was associated with a significant decrease in angiotensin I-converting enzyme activity and a small, but significant, increase in neutral endopeptidase 24.11 activity in the cheek pouch, two peptidases widely distributed in the microcirculation that cleave and inactivate bradykinin (p < 0.05). Overall, these data suggest that smokeless tobacco elicits plasma exudation in the oral mucosa in vivo in a specific fashion, and that this response is mediated by bradykinin.

AB - The purpose of this study was to determine whether an aqueous extract of smokeless tobacco (moist snuff) increases clearance of macromolecules from postcapillary venules in the in situ oral mucosa and, if so, whether bradykinin mediated this response. Using intravital microscopy, we found that 20-min suffusion of the extract elicited significant concentration-dependent leaky site formation and increase in clearance of FITC-dextran (molecular mass, 70 kDa) from the hamster cheek pouch (p < 0.05). These responses were associated with a significant increase in bradykinin-like immunoreactivity in the suffusate. Smokeless tobacco extract-induced leaky site formation and increase in clearance of FITC-dextran were significantly attenuated by NPC 17647 and Hoe 140 (p < 0.05), two bradykinin B2 receptor antagonists, but not by desArg9,[Leu8]bradykinin, a bradykinin B1 receptor antagonist. Both bradykinin B2 receptor antagonists had no significant effects on adenosine-induced responses. Indomethacin had no significant effects on smokeless tobacco extract-induced responses. Exposure to smokeless tobacco extract was associated with a significant decrease in angiotensin I-converting enzyme activity and a small, but significant, increase in neutral endopeptidase 24.11 activity in the cheek pouch, two peptidases widely distributed in the microcirculation that cleave and inactivate bradykinin (p < 0.05). Overall, these data suggest that smokeless tobacco elicits plasma exudation in the oral mucosa in vivo in a specific fashion, and that this response is mediated by bradykinin.

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