Anti-inflammatory action of dapsone: inhibition of neutrophil adherence is associated with inhibition of chemoattractant-induced signal transduction.
Dapsone has clinical utility as an anti-inflammatory agent but the mechanism of this action remains unknown. We have previously reported that dapsone inhibits beta2 integrin (CD11b/CD18)-mediated adherence of human neutrophils in vitro and now describe studies designed to discover how dapsone-mediated inhibition of this neutrophil function occurs. Results indicate that dapsone interferes with the activation or function of the G-protein (Gi type) that initiates the signal transduction cascade common to chemotactic stimuli. They also show that dapsone-mediated suppression of this pathway inhibits the generation of second messengers essential to the activation of beta2 integrin molecules, as well as respiratory and secretory functions of neutrophils exposed to chemoattractants. We propose that the inhibition of chemoattractant-induced signal transduction by dapsone suppresses neutrophil recruitment and local production of toxic respiratory and secretory products in the affected skin of dermatitis herpetiformis and other neutrophilic dermatoses.
Debol
S M
SM
Department of Microbiology, University of Minnesota Medical School, Minneapolis 55455-0392, USA.
Herron
M J
MJ
Nelson
R D
RD
D000890:Anti-Infective Agents / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000494:pharmacology; D003622:Dapsone / Q000494:pharmacology*; D004347:Drug Interactions; D006801:Humans; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
D000890:Anti-Infective Agents; D000893:Anti-Inflammatory Agents; D002630:Chemotactic Factors; D003622:Dapsone