Alveolar Proteinosis and Phospholipidoses of the Lungs*1

Abstract

Three pulmonary disease conditions result from the accumulation of phospholipids in the lung. These conditions are the human lung disease known as pulmonary alveolar proteinosis, the lipoproteinosis that arises in the lungs of rats during acute silicosis, and the phospholipidoses induced by numerous cationic amphiphilic therapeutic agents. In this paper, the status of phospholipid metabolism in the lungs during the process of each of these lung conditions has been reviewed and possible mechanisms for their establishment are discussed. Pulmonary alveolar proteinosis is characterized by the accumulation of tubular myelin-like multilamellated structures in the alveoli and distal airways of patients. These structures appear to be formed by a process of spontaneous assembly involving surfactant protein A and surfactant phospholipids. Structures similar to tubular myelin-like multilamellated structures can be seen in the alveoli of rats during acute silicosis and, as with the human condition, both surfactant protein A and surfactant phospholipids accumulate in the alveoli. Excessive accumulation of surfactant protein A and surfactant phospholipids in the alveoli could arise from their overproduction and hypersecretion by a subpopulation of Type II cells that are activated by silica, and possibly other agents. Phospholipidoses caused by cationic amphiphilic therapeutic agents arise as a result of their inhibition of phospholipid catabolism. Inhibition of phospholipases results in the accumulation of phospholipids in the cytoplasm of alveolar macrophages and other cells. While inhibition of phospholipases by these agents undoubtedly occurs, there are many anomalous features, such as the accumulation of extracellular phospholipids and surfactant protein A, that cannot be accounted for by this simplistic hypothesis.

Palmitic Acid: Physiological Role, Metabolism and Nutritional Implications

“…Pulmonary surfactant presents different classes of lipids, such as PL, TAG, cholesterol, and FA and surfactant-associated proteins that extensively interact with PL regulating structure and properties of the lipid film (Yu and Possmayer, 1988 ; Jobe and Ikegami, 2001 ; Suresh and Soll, 2001 ; Ainsworth and Milligan, 2002 ). The PL composition of surfactant is highly conserved among mammals (Hook, 1991 ; Sullivan et al, 2002 ). PC is the main PL covering 80% of surfactant lipids with dipalmitoylphosphatidylcholine (DPPC, 16:0/16:0-PC), the principal surface-active component, accounting for 60% (Thannhauser et al, 1946 ; Kahn et al, 1995 ; Creuwels et al, 1997 ; Jobe and Ikegami, 2001 ; Suresh and Soll, 2001 ).…”

Surfactant phospholipid metabolism

“…Surfactant also contains the key surfactant proteins A, B, C, and D (SP-A, SP-B, SP-C, and SP-D) (Fig 1). The phospholipid composition of surfactant is highly conserved among mammals [7, 8]. Phosphatidylcholine (PC) is the major phospholipid comprising 80% of surfactant lipids.…”

“…It is estimated that ~45% of surfactant DPPC is formed via de novo synthesis, while the other 55%–75% is generated by remodeling [9, 99, 100]. This remodeling pathway is catalyzed by a series of enzymatic reactions involving phospholipase A 2 (PLA 2 ) mediated hydrolysis of unsaturated fatty acids at the sn -2-position of PC generating lyso-PC followed by re-acylation with saturated (16:0) species yielding DPPC [7, 101, 102] (Fig. 2C).…”

International Harmonization of Nomenclature and Diagnostic Criteria (INHAND): Nonproliferative and Proliferative Lesions of the Dog

“…The term alveolar phospholipidosis is not a synonym for increased alveolar macrophages and should be reserved for accumulations of phospholipid-containing macrophages observed after treatment with cationic amphiphilic drugs. 175,176 Metaplasia, Osseous-Lung: Alveoli…”