Linked Life Data

3871198

Source:http://linkedlifedata.com/resource/pubmed/id/3871198

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1985-2-15
pubmed:abstractText
Adenosine (Ado), deoxyadenosine (dAdo), and adenine arabinoside (AraA) inhibit the phagocytosis of IgG-coated erythrocytes and zymosan by resident and thioglycollate-elicited macrophages (thio-macrophages) in a dose-dependent and reversible manner. 3-Deazaadenosine (3cAdo) and adenine (Ade) also inhibit the phagocytosis by resident macrophages. Homocysteine thiolactonate (Hcy) potentiates the inhibition by Ado and 3cAdo while erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) potentiates the inhibition by Ado, dAdo and AraA. This inhibition has a very rapid onset and the drugs do not interfere with the binding of IgG-coated erythrocytes to macrophages. The combination of Ado, Hcy and EHNA does not appreciably affect the intracellular level of ATP and S-adenosyl-L-methionine (AdoMet) in thio-macrophages but causes accumulations of Ado and S-adenosyl-L-homocysteine (AdoHcy) up to 135 and 145 nmol/mg of protein, respectively. During phagocytosis reversal, Ado is metabolized within 15 min while AdoHcy decreases log-arithmically with a half-life of 50 min. Carboxymethylation and phospholipid methylation, however, resume about 60-90 min after phagocytosis has recovered, and thus cannot function as transmembrane signals for phagocytosis. Other evidence showing the lack of correlation between phagocytosis and carboxymethylation inhibition include 1) Ado + Hcy inhibit carboxymethylation much better than Ado + EHNA (91 versus 75%) in thio-macrophage, but the two combinations show comparable phagocytosis inhibition potency; 2) Ado + Hcy inhibit carboxymethylation almost as well as Ado + Hcy + EHNA, but the latter is a much more effective drug combination for phagocytosis inhibition; 3) Ade and 3cAdo, although inhibiting resident macrophage phagocytosis as well as Ado + EHNA + Hcy, are much weaker carboxymethylation inhibitors; 4) dAdo and AraA potently inhibit phagocytosis but not carboxymethylation. The difference in the apparent methylation levels is not due to changes in the specific activities of AdoMet, which decrease with a half-life of 88 min. Interestingly, after the initial lag phase of about 90 min after the initiation of inhibition reversal, carboxymethylation and phagocytosis increase in parallel. In a log-log plot of carboxymethylation, phospholipid methylation, or phagocytosis versus the intracellular AdoHcy accumulation, a linear relationship is obtained. It is possible that AdoHcy accumulation is responsible for phagocytosis inhibition but inhibits by a mechanism other than interfering with protein and lipid methylations.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
260
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
546-54
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1985
pubmed:articleTitle
Inhibition of macrophage phagocytosis by methylation inhibitors. Lack of correlation of protein carboxymethylation and phospholipid methylation with phagocytosis.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.