Characterization of the third component of complement (C3) after activation by cigarette smoke
Activation of lung complement by tobacco smoke may be an important pathogenetic factor in the development of pulmonary emphysema in smokers. We previously showed that cigarette smoke can modify C3 and activate the alternative pathway of complement in vitro. However, the mechanism of C3 activation was not fully delineated in these earlier studies. In the present report, we show that smoke-treated C3 induces cleavage of the alternative pathway protein, Factor B, when added to serum containing Mg-EGTA. This effect of cigarette smoke is specific for C3 since smoke-treated C4, when added to Mg-EGTA-treated serum, fails to activate the alternative pathway and fails to induce Factor B cleavage. Smoke-modified C3 no longer binds significant amounts of (/sup 14/C)methylamine (as does native C3), and relatively little (/sup 14/C)methylamine is incorporated into its alpha-chain. Thus, prior internal thiolester bond cleavage appears to have occurred in C3 activated by cigarette smoke. Cigarette smoke components also induce formation of noncovalently associated, soluble C3 multimers, with a Mr ranging from 1 to 10 million. However, prior cleavage of the thiolester bond in C3 with methylamine prevents the subsequent formation of these smoke-induced aggregates. These data indicate that cigarette smoke activates the alternative pathway of complement by specifically modifying C3 and that these modifications include cleavage of the thiolester bond in C3 and formation of noncovalently linked C3 multimers.
- Research Organization:
- State Univ. of New York, Stony Brook
- OSTI ID:
- 6177033
- Journal Information:
- Clin. Immunol. Immunopathol.; (United States), Vol. 44:2
- Country of Publication:
- United States
- Language:
- English
Similar Records
Effect of cigarette smoke on human serum trypsin inhibitory capacity and antitrypsin concentration
Mice overexpressing latent matrix metalloproteinase-2 develop lung emphysema after short-term exposure to cigarette smoke extract
Related Subjects
COMPLEMENT
BIOLOGICAL PATHWAYS
CHEMICAL COMPOSITION
EMPHYSEMA
PATHOGENESIS
PROTEINS
CLEAVAGE
CARBON 14 COMPOUNDS
CYSTEINE
LUNGS
METHYLAMINE
MOLECULAR WEIGHT
TOBACCO SMOKES
TRACER TECHNIQUES
AEROSOLS
AMINES
AMINO ACIDS
BODY
CARBOXYLIC ACIDS
COLLOIDS
CRYSTAL STRUCTURE
DISEASES
DISPERSIONS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MICROSTRUCTURE
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
RESIDUES
RESPIRATORY SYSTEM
RESPIRATORY SYSTEM DISEASES
SMOKES
SOLS
THIOLS
550901* - Pathology- Tracer Techniques