ACTIVATION OF THE CLASSICAL PATHWAY OF COMPLEMENT BY TOBACCO GLYCOPROTEIN (TGP)

Tobacco glycoprotein (TGP), a polyphenol-rich glycoprotein isolated fr om tobacco leaves, activates the classical complement pathway through a mechanism that appears to involve direct interaction with C1q. A bin ding site on C1q for TGP can be localized by competitive inhibition wi th DNA to a region located in the junction between the collagen-like a nd globular regions of the molecule. A protein with activity similar t o TGP has also been isolated from cigarette smoke condensate (TGP-S); it shares a binding site on C1q with TGP and has similar functional ac tivity, with the exception that complement activation does not proceed to formation of a C3 cleaving enzyme. The ability of TGP and TGP-S to activate complement can be partially duplicated using polyphenols ass ociated with tobacco leaf and smoke, i.e., chlorogenic acid and rutin. These polyphenols also compete with TGP for a binding site on immobil ized C1q, suggesting that the polyphenol portion of TGP is critical fo r activation of complement. These results provide an additional mechan ism for complement activation by cigarette products that, in vivo, cou ld result in a localized complement depletion, generation of biologica lly active complement cleavage products, and initiation of an inflamma tory response.