Activation of the classical pathway of complement by tobacco glycoprotein (TGP).
Tobacco glycoprotein (TGP), a polyphenol-rich glycoprotein isolated from tobacco leaves, activates the classical complement pathway through a mechanism that appears to involve direct interaction with C1q. A binding site on C1q for TGP can be localized by competitive inhibition with DNA to a region located in the junction between the collagen-like and globular regions of the molecule. A protein with activity similar to TGP has also been isolated from cigarette smoke condensate (TGP-S); it shares a binding site on C1q with TGP and has similar functional activity, 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 associated with tobacco leaf and smoke, i.e., chlorogenic acid and rutin. These polyphenols also compete with TGP for a binding site on immobilized C1q, suggesting that the polyphenol portion of TGP is critical for activation of complement. These results provide an additional mechanism for complement activation by cigarette products that, in vivo, could result in a localized complement depletion, generation of biologically active complement cleavage products, and initiation of an inflammatory response.
Koethe
S M
SM
Department of Pathology, Medical College of Wisconsin, Milwaukee 53226, USA.
Nelson
K E
KE
Becker
C G
CG
D003167:Complement Activation / Q000187:drug effects*; D003174:Complement C1 Inactivator Proteins / Q000502:physiology; D015922:Complement C1q / Q000378:metabolism; D003171:Complement Pathway, Classical / Q000187:drug effects; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D010636:Phenols / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D010940:Plant Proteins / Q000737:chemistry; D010947:Plants, Toxic; D012906:Smoke / Q000032:analysis; D014026:Nicotiana / Q000737:chemistry
D003174:Complement C1 Inactivator Proteins; D006023:Glycoproteins; D010636:Phenols; D010940:Plant Proteins; D012906:Smoke; C046039:TGP protein, Nicotiana tabacum; D015922:Complement C1q