Expression of fatty‐acid‐binding proteins in cells involved in lung‐specific lipid metabolism

Abstract

Members of the fatty-acid-binding protein (FABP) family are thought to play an important role in fatty acid transport within the cytosol and thus to be involved in lipid metabolism. As previous data on the occurrence of distinct FABP types in total lung are contradictory, we determined the expression of FABP types in three isolated cell types of rat lung, which are characterised by active lipid metabolism. Alveolar type-II cells synthesise, store and secrete pulmonary surfactant, a phospholipid-rich surfacetension-lowering agent, whereas lung fibroblasts, localised adjacent to the alveolar type-II cells, are assumed to provide neutral lipid substrate to alveolar type-II cells around birth, and alveolar macrophages are known to degrade complex lipids. Initial screening by reverse transcriptase PCR revealed the occurrence of heart (H-), epidermal (E-) and liver FABP in rat lung, the latter being not detectable in the three cell types studied. Cells were analysed by northern and western blotting, then quantitatively by sandwich ELISA, for which recombinant rat E-FABP was prepared. E-FABP mRNA was found in all three cell types, and E-FABP was detected in the following amounts: 240.9Ϯ19.0 ng/mg cytosolic protein in alveolar type-II cells; 172.3Ϯ0.7 ng/mg protein for lung fibroblasts ; and 36.9 Ϯ3.5 ng/mg protein for alveolar macrophages. This indicates a basic function of E-FABP in cellular lipid metabolism. In contrast, H-FABP probably is involved in the metabolism of neutral lipids because H-FABP mRNA was found only in lung fibroblasts with a corresponding protein level of 315.5Ϯ6.9 ng/mg. Small amounts of H-FABP protein were present in alveolar type-II cells and alveolar macrophages.Keywords : fatty-acid-binding protein; alveolar type-II cell; lung fibroblast ; alveolar macrophage; ELISA.In rat lung, alveolar type-II cells synthesise, store and secrete thought to be involved in a facilitated on-demand supply of surfactant substrate [9]. pulmonary surfactant, a phospholipid · protein complex that preParticipation of alveolar macrophages in surfactant metabovents the collapse of the alveoli by reducing surface tension at lism was suggested from in vivo and in vitro experiments [10Ϫ the air-liquid interface. This surfactant is highly enriched in 12]. Theoretically, alveolar macrophages could account for the phospholipids, particularly dipalmitoyl phosphatidylcholine.entire catabolism of alveolar surfactant in rat lung [11]. Fatty Fatty acids required for the biosynthesis of phospholipids are acids derived from phosphatidylcholine degradation are reused either synthesised de novo within this type-II cell [1Ϫ3] or taken for triacylglycerol synthesis [13]. up from exogenous sources [4Ϫ6]. Uptake and intracellular It is obvious from the above that fatty acids are needed for transfer of fatty acids by these alveolar type-II cells are not well lung surfactant homeostasis, in which the three cell types menunderstood [7], but the high turnover of phospholipids requires tioned appear to be involved. As a consequence, fatty ac...

FABP5 deficiency enhances susceptibility to H1N1 influenza A virus-induced lung inflammation

“…Similar upregulation was observed in alveolar macrophages following acute lung rejection (20). As mentioned previously, FABP5 is highly expressed in bronchial epithelial cells, alveolar type II epithelial cells, lung fibroblasts, and alveolar macrophages (15,16,33). Given this large array of expression in different lung cell types, we performed coimmunostaining of FABP5 with alveolar macrophages, airway epithelial cells, and type I and type II alveolar epithelial cells.…”

“…The FABP5 gene encodes the epidermal fatty acid binding protein and was first found to be upregulated in psoriasis tissue (41). In the lung, FABP5 is mainly expressed by bronchial epithelial cells, alveolar type II epithelial cells, alveolar macrophages, and fibroblasts (15,16,33). FABP5 is upregulated in alveolar macrophages during acute lung rejection (20).…”

Genetic Analysis of Congenital Cystic Adenomatoid Malformation Reveals a Novel Pulmonary Gene: Fatty Acid Binding Protein-7 (Brain Type)

“…Both FABP-3 (heart type, or H-FABP) and FABP-5 (epidermal type, or E-FABP) were found by RT-PCR to be expressed in the lung (21,22). Northern blot analysis showed H-FABP to be restricted to lung fibroblasts, and E-FABP to be present in type II cells, lung fibroblasts, and in macrophages (22). FABP-7 expression was examined at weeks 9 -10 of human fetal lung, and found not to be expressed (19).…”

“…A FABP-5/ FABP-3 double-knockout mouse was generated, and type II cells were analyzed from the wildtype and double-knockout mice. The double-knockout mice resulted in impaired surfactant synthesis with a decrease in palmitate uptake, ␤-oxidation, and incorporation of neutral lipids and phosphatidylcholine of type II cells (22).…”

Fatty acid binding proteins stabilize leukotriene A4

“…Only A-FABP and E-FABP have been shown to be expressed in cells of the myeloid lineage, which can produce LTA 4 (25,26), and perhaps these FABPs play a role in facilitating the distribution of LTA 4 within these cells. The other FABP family members could still play some role in Fig.…”