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Effect of ethanol on thrombopoiesis
Author(s) -
Levine Richard F.,
Spivak Jerry L.,
Meagher Richard C.,
Sieber Fritz
Publication year - 1986
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1986.tb02938.x
Subject(s) - megakaryocyte , thrombopoiesis , acetaldehyde , ethanol , chemistry , incubation , biochemistry , microbiology and biotechnology , biology , progenitor cell , stem cell
S ummary . Chronic ethanol abuse causes thrombocytopenia but the underlying mechanism is unknown. To determine the target cells involved, we examined the effects of the drug in vitro on both megakaryocyte progenitor cells (CFU‐Meg) and isolated, maturing megakaryocytes. In the presence of ethanol concentrations of 0.05–2.0 g/dl, megakaryocyte colony formation by mouse CFU‐Meg in soft agar was normal. At 5 g/dl ethanol, colony formation was reduced by 50%; with 7 g/dl ethanol, no megakaryocyte colonies were formed. Acetaldehyde did not inhibit colony formation unless very high concentrations (100 mg/dl) were employed. Isolated guinea‐pig megakaryocytes can maintain their viability and incorporate 3 H‐leucine into TCA‐precipitable protein for at least 24 h. Incubation of these maturing megakaryocytes with ethanol did not affect their viability, but at concentrations greater than 120 mg/dl ethanol progressively inhibited protein synthesis. At 0.5 g/dl ethanol, protein synthesis was decreased by 23% while viability was still 93% of control. Like CFU‐Meg, maturing megakaryocytes were resistant to the toxic effects of acetaldehyde. To determine the in vivo correlates of these results, guinea‐pigs were fed 5 g/dl ethanol in a liquid diet. by 11 d, when blood ethanol levels were 20–150 mg/dl, platelet counts in the animals were reduced by 17–29%, while the number of marrow megakaryocytes was unaltered. These data indicate that the site of action of ethanol in suppressing thrombopoiesis is at the level of the maturing megakaryocyte.