Document Detail


Inhibitors of monocyte responses to chemotaxins are present in human cancerous effusions and react with monoclonal antibodies to the P15(E) structural protein of retroviruses.
MedLine Citation:
PMID:  7026615     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Individuals with cancer have previously been shown to have abnormal chemotactic responsiveness. Surgical removal of the tumor often resulted in normalization of monocyte function, which suggests that human neoplasms might inhibit monocyte chemotaxis by release of soluble mediators. We therefore examined the effects of cancerous effusions on monocyte polarization, i.e., the rapid change in monocyte morphology from round to a triangular "motile" configuration in response to chemoattractants. All 17 malignant effusions, representing 15 tumor types, inhibited monocyte polarization induced by the chemoattractant N-formyl-methionyl-leucyl-phenylalanine by 45-89% (mean 55.9 +/- 12.7%, P less than 0.01) in blinded assays. None of 17 benign effusions signigicantly inhibited polarization (0-15%, mean 6.2 +/- 4.2%). Dilutions of cancerous effusions as low as 1:200 produced inhibition that was time, temperature, and dose dependent . Monocyte polarization induced by activated serum or by chemotactic lymphokine was also blocked by cancerous effusions. The inhibitory activity affected the monocyte directly, and did not destroy the chemoattractant or block the polarization of granulocytes to chemotactic factors. High pressure liquid chromatography of five cancerous fluids revealed three peaks of inhibitory activity: greater than or equal to 200,000, 46,000 +/- 13,000, and 21,000 +/- 3,000 daltons. Fractionation of noncancerous effusions revealed only small amounts of the highest molecular weight inhibitory activity. The inhibitory activity in cancerous effusion was heat stable (56 degrees C, 30 min), trypsin sensitive, and could be absorbed by three different monoclonal antibodies reactive to P15(E), a structural component of type C retroviruses. In contrast, six monoclonal antibodies with other specificities had no effect on the inhibitors of polarization. This study demonstrates that human cancerous effusions contain novel proteins that are potent inhibitors of monocyte function and that are recognized by antibodies reactive to the P15(E) component of retroviruses. By producing such factors, tumor cells may subvert monocyte-mediated surveillance.
Authors:
G Cianciolo; J Hunter; J Silva; J S Haskill; R Snyderman
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  68     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1981 Oct 
Date Detail:
Created Date:  1981-12-21     Completed Date:  1981-12-21     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  831-44     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Antibodies, Monoclonal
Antibodies, Viral
Ascites / immunology
Chemotaxis, Leukocyte*
Exudates and Transudates / immunology
Female
Humans
Immune Tolerance
Male
Middle Aged
Monocytes / immunology*
Neoplasms / immunology*
Peptide Hydrolases / metabolism
Pleural Effusion / immunology
Retroviridae / immunology*
Temperature
Viral Proteins / immunology*
Grant Support
ID/Acronym/Agency:
N01-CB-74121/CB/NCI NIH HHS; ST32-CA09307/ST/OHS HRSA HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antibodies, Viral; 0/Viral Proteins; EC 3.4.-/Peptide Hydrolases
Comments/Corrections

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