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Multinucleation in alveolar macrophages from rats treated with chlorphentermine.

Reasor-MJ; Massey-CA; Koshut-RA; Castranova-V
Lab Invest 1982 Jan; 46(2):224-230
The effect of chlorphentermine (461789) (CP) on alveolar macrophages as a function of time was investigated in rats. Male Long-Evans- hooded-rats were given 30 milligrams per kilogram CP intraperitoneally, 5 days a week for 1 to 4 weeks. Animals were killed and alveolar macrophages were collected by pulmonary lavage and counted. Macrophages were separated into 4 fractions of elutriation. Cell numbers in each fraction were counted and sized. Phospholipid content was determined by extraction of cells with chloroform and methanol and protein and DNA were measured. Nuclei in each cell were also counted. CP induced an increase in total protein contents of macrophages which was directly proportional to duration of drug treatment. After 1 week of treatment there was a 10 fold increase in phospholipids in macrophages which continued through the 4 weeks of treatment. Protein increases followed the same pattern as phospholipids, with the largest increase occurring 1 week after CP treatment. A similar increase was observed in multinucleate macrophages lavaged from the lungs during phospholipid induction over the same period. This increase was also progressive up to 10 nuclei. There was a significant increase in DNA content at the end of the 4 weeks of CP treatment. This increase correlated well with the increase in multinucleation. There was a 24 percent increase in the nuclei population while DNA content increased 32 percent over control values. The DNA increase was accompanied by protein and RNA increase which gave high RNA/DNA and protein/RNA ratios. Weekly mean volumes of cells increased with increasing fraction number. Increase in phospholipids and protein was only seen in fraction 4 after 4 weeks of treatment. The authors interpret the mechanism of multinucleation to be due to failure of cells to divide following mitosis.
Alveolar-cells; Biological-effects; Cell-division; Mitosis; Lipid-disorders; Drug-therapy; Physiological-response; Pharmacology; Phospholipids
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Laboratory Investigation