Hemoglobin Is Expressed by Alveolar Epithelial Cells

Abstract

Hemoglobin gene expression in non-erythroid cells has been previously reported in activated macrophages from adult mice and lens cells, and recent studies indicate that alveolar epithelial cells can be derived from hematopoietic stem cells. Our laboratory has now produced strong evidence that hemoglobin is expressed by alveolar type II (ATII) cells and Clara cells, the primary producers of pulmonary surfactant. ATII cells are also closely involved in innate immunity within the lung and are stem cells that differentiate into alveolar type I cells. Reverse transcriptase-PCR was used to measure the expression of transcripts from the ␣-and ␤-globin gene clusters in several human and rodent pulmonary epithelial cells. Surprisingly, the two major globin mRNAs characteristic of adult erythroid precursor cells were clearly expressed in human A549 and H441 cell lines, mouse MLE-15 cells, and primary ATII cells isolated from normal rat and mouse lungs. DNA sequencing verified that these PCR products were indeed the result of specific amplification of globin gene cDNAs. These alveolar epithelial cells also expressed the corresponding hemoglobin protein subunits as determined by Western blotting, and tandem mass spectrometry sequencing was used to verify the presence of both ␣-and ␤-globin polypeptides in rat primary ATII cells. The function of hemoglobin expression by cells of the pulmonary epithelium will be determined by future studies, but this novel finding could potentially have important implications for the physiology and pathology of the lung.

Identification of genes selectively disallowed in the pancreatic islet

“…The list of probesets was then filtered to remove any probesets that had been removed from our analysis during genuine signals rather than an artefact. In recent years there have been a growing number of reports of hemoglobin expression in a range of other tissues including neurons, 14 macrophages, 15 alveolar epithelial cells, 16 lens 17 and myelin. 18 This suggests that hemoglobin may play a more general role in oxygen balance within many cell types.…”

Androgen receptor and androgen-dependent gene expression in lung

“…Hemoglobin genes are expressed, not only in blood cells, but also in cultured PTII and Clara cells (Newton et al, 2006), and cellular hemoglobin is proposed to serve as a protective agent against oxidative and nitrosative stress (Liu et al, 2000;Minning et al, 1999). Androgen treatment not only increased expression of genes involved in oxygen transport, such as those encoding hemoglobins, but it also decreased expression of genes involved in DNA damage repair.…”

Maternal administration of nanomaterials elicits hemoglobin upregulation in the neonatal brain of non-human primates

“…Hemoglobin is expressed in tissues other than erythrocytes, including the brain (Richter et al, 2009), LPS-treated macrophages (Liu et al, 1999), and alveolar epithelial cells (Newton et al, 2006). In the brain, the tetrameric structure of hemoglobin (which is comprised of alpha and beta globin chains) and its expression is related to oxygen homeostasis and oxidative phosphorylation (Biagioli et al, 2009 PNAS;Russo et al, 2013 BBA).…”