Drug-induced lipidosis and the alveolar macrophage.
The alveolar macrophage is the principal component of the defense mechanisms of the lung. As a result, alterations in its function can predispose the host organism to pulmonary disease or damage. This cell shows toxic responses to a wide variety of chemicals which are delivered to the lungs by either inhalation or via the systemic circulation. In this regard, this review will focus on the effects of a group of cationic amphiphilic drugs which when administered to humans and animals causes a lysosomal storage disorder of lipids, principally phospholipids, in alveolar macrophages. The susceptibility to the disorder is species-dependent and can be induced in fetal, neonatal and adult animals. Evidence exists that the accumulation of lipids within the cells occurs as a result of an impairment in lipid catabolism, however, not all of the available data are consistent with this theory. In light of this, other mechanisms to explain the etiology of this lipidosis are discussed. Associated with the increase in lipid content within the cell, striking morphological, biochemical and functional changes occur to the alveolar macrophage. Available data indicate that afflicted cells have an increased phagocytic activity and exhibit enhanced killing of one strain of bacteria. While these data suggest an enhancement in certain cellular functions, inadequate information presently exists to allow conclusions to be drawn concerning the consequences of this disorder.
D000818:Animals; D002745:Chlorphentermine / Q000633:toxicity; D006801:Humans; D008054:Lipid Peroxides / Q000378:metabolism; D008064:Lipidoses / Q000139:chemically induced*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010587:Phagocytosis; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010743:Phospholipids / Q000032:analysis / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats
D008054:Lipid Peroxides; D004364:Pharmaceutical Preparations; D010743:Phospholipids; D006899:Mixed Function Oxygenases; D002745:Chlorphentermine