Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 [14C]methylamine (as does native C3), and relatively little [14C]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.
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PMID:Characterization of the third component of complement (C3) after activation by cigarette smoke. 364 80

Elastase, released by stimulated polymorphonuclear leukocytes (PMN), is thought to play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD) especially pulmonary emphysema. A test that can detect release of elastase activity from PMN would be valuable to monitor therapy or to identify patients at risk. The authors aimed to isolate and characterize monoclonal antibodies (mAb) with a high affinity for a neo-antigenic determinant in a high-molecular weight degradation product of fibrinogen (Fbg) generated by PMN-derived elastase. Using synthetic peptides, they mimicked the new amino or carboxy terminal sequences of the A alpha-, B beta- and gamma-chains of Fbg that are generated by elastase. These synthetic peptides (A alpha 22-36, A alpha 350-360, B beta 44-55, and gamma 295-305), uni-directionally coupled to a carrier protein, were used to generate mAb specific for elastase-degraded fibrinogen (EDF). mAb that appeared to be specific for a neo-antigenic determinant (neotope) consisting of the new amino terminal amino acid(s) of the Fbg A alpha-chain that is generated by elastase activity were isolated only with the A alpha 22-36 synthetic peptide. One mAb, designated as EF1-4, was further characterized and had an approximately 75-fold higher affinity for EDF, as compared with Fbg, in solution. Using the other peptides, no mAb specific for elastase generated fibrinogen degradation products were obtained.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A monoclonal antibody with high affinity for a neo-antigenic site in fibrinogen degraded by polymorphonuclear leukocyte-derived elastase. 754 37