Hemoglobin α and β are ubiquitous in the human lung, decline in idiopathic pulmonary fibrosis but not in COPD.
BACKGROUND
Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are disorders of the lung parenchyma. They share the common denominators of a progressive nature and poor prognosis. The goal was to use non-biased proteomics to discover new markers for these diseases.


METHODS
Proteomics of fibrotic vs. control lung tissue suggested decreased levels of several spots in the lung specimens of IPF patients, which were identified as Hemoglobin (Hb) α and β monomers and Hbα complexes. The Hbα and β monomers and complexes were investigated in more detail in normal lung and lung specimens of patients with IPF and COPD by immunohistochemistry, morphometry and mass spectrometry (MS).


RESULTS
Both Hb monomers, in normal lung, were expressed especially in the alveolar epithelium. Levels of Hbα and β monomers and complexes were reduced/lost in IPF but not in the COPD lungs when compared to control lung. MS-analyses revealed Hbα modification at cysteine105 (Cysα105), preventing formation of the Hbα complexes in the IPF lungs. Hbα and Hbβ were expressed as complexes and monomers in the lung tissues, but were secreted into the bronchoalveolar lavage fluid and/or induced sputum supernatants as complexes corresponding to the molecular weight of the Hb tetramer.


CONCLUSIONS
The abundant expression of the oxygen carrier molecule Hb in the normal lung epithelium and its decline in IPF lung are new findings. The loss of Hb complex formation in IPF warrants further studies and may be considered as a disease-specific modification.
Ishikawa
Nobuhisa
N
Department of Medicine, Pulmonary Division, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
Ohlmeier
Steffen
S
Salmenkivi
Kaisa
K
Myllärniemi
Marjukka
M
Rahman
Irfan
I
Mazur
Witold
W
Kinnula
Vuokko L
VL
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D003937:Diagnosis, Differential; D005260:Female; D006454:Hemoglobins / Q000096:biosynthesis*; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000097:blood; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D055544:beta-Globins / Q000096:biosynthesis*
D015415:Biomarkers; D006454:Hemoglobins; D010446:Peptide Fragments; C443665:beta(A-T87Q) globin; D055544:beta-Globins; C059146:hemoglobin alpha-chain fragments (123-136)