BPIFB1 (LPLUNC1) is upregulated in cystic fibrosis lung disease

• Main Authors: Araujo, B. (Author), Bingle, C.D (Author), Bingle, L. (Author), LeClair, E.E (Author), Mall, M.A (Author), Mauad, T. (Author), Musa, M. (Author), Rassl, D. (Author), Wallace, W.A (Author), Wilson, K. (Author), Zhou, Z. (Author)
• Format: Article
• Language: English
• Subjects: Airway; airway remodeling; animal cell; animal experiment; animal model; animal tissue; Animals; Antigens, CD; Antigens, Differentiation, Myelomonocytic; article; Bacteria (microorganisms); bpifa1 protein; BPIFB1; bpifb1 protein; Bronchoalveolar Lavage Fluid; Carrier Proteins; controlled study; cystic fibrosis; Cystic fibrosis; Cystic Fibrosis; Disease Models, Animal; disease severity; epithelial sodium channel; Epithelial Sodium Channels; Glycoproteins; goblet cell; Goblet Cells; human; human cell; Humans; immunohistochemistry; Immunohistochemistry; Leukocytes, Mononuclear; LPLUNC1; Lung; lung alveolus macrophage; lung fibrosis; lung parenchyma; Mice; Mice, Inbred C57BL; Mice, Transgenic; mouse; Mouse models; Mucin 5AC; Mus; neutrophil; Neutrophils; nonhuman; peripheral blood mononuclear cell; Phosphoproteins; Pneumonia, Bacterial; priority journal; protein; protein expression; protein localization; protein synthesis; Proteins; respiratory system; transgenic mouse; unclassified drug; Up-Regulation
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 Although the biology the PLUNC (recently renamed BPI fold, BPIF) family of secreted proteins is poorly understood, multiple array based studies have suggested that some are differentially expressed in lung diseases. We have examined the expression of BPIFB1 (LPLUNC1), the prototypic two-domain containing family member, in lungs from CF patients and in mouse models of CF lung disease. BPIFB1 was localized in CF lung samples along with BPIFA1, MUC5AC, CD68 and NE and directly compared to histologically normal lung tissues and that of bacterial pneumonia. We generated novel antibodies to mouse BPIF proteins to conduct similar studies on ENaC transgenic (ENaC-Tg) mice, a model for CF-like lung disease. Small airways in CF demonstrated marked epithelial staining of BPIFB1 in goblet cells but staining was absent from alveolar regions. BPIFA1 and BPIFB1 were not co-localised in the diseased lungs. In ENaC-Tg mice there was strong staining of both proteins in the airways and luminal contents. This was most marked for BPIFB1 and was noted within 2 weeks of birth. The two proteins were present in distinct cells within epithelium. BPIFB1 was readily detected in BAL from ENaC-Tg mice but was absent from wild-type mice. Alterations in the expression of BPIF proteins is associated with CF lung disease in humans and mice. It is unclear if this elevation of protein production, which results from phenotypic alteration of the cells within the diseased epithelium, plays a role in the pathogenesis of the disease. © The Author(s) 2012.