Bronchoalveolar Lavage Fluid Surfactant Protein-A and Surfactant Protein-D Are Inversely Related to Inflammation in Early Cystic Fibrosis

Abstract

The pulmonary collectins surfactant protein (SP)-A and SP-D play important roles in innate lung defense, enhancing opsonization of microbes and limiting lung inflammatory responses. To quantify relationships among collectins, bacteria, and inflammation in early cystic fibrosis (CF) airway secretions, bronchoalveolar lavage fluids (BALFs) were collected from children undergoing clinically indicated bronchoscopy. Quantitative bacteriology, differential cell counts, and ELISA for SP-A and SP-D were assessed. Significantly increased numbers of neutrophils relative to bacteria were noted in BALF from CF compared with non-CF subjects. Although SP-A levels tended to be lower in CF compared with non-CF, this was only significant in the presence of bacterial infection. Among CF patients, SP-A concentrations in BALF were inversely related to inflammation, bacterial colony-forming units per milliliter, and age. SP-D levels were significantly decreased in CF patients, and SP-D was rarely detectable in the presence of infection. Among CF patients, SP-D correlated inversely with inflammation and bacterial colony-forming units per milliliter, and there was decreased immunostaining of BALF cells for SP-D in CF. Immunohistochemistry of CF autopsy lung sections for SP-A and SP-D confirmed their paucity at sites of infection and inflammation. We conclude that relative collectin deficiency occurs early in CF airways and is inversely related to inflammation in CF airways.

KL-6 and Surfactant Proteins A and D in Serum and Bronchoalveolar Lavage Fluid in Patients with Acute Eosinophilic Pneumonia

“…On the other hand, SP-A or SP-D levels in BALF from patients with IPF or interstitial pneumonia with collagen vascular disease (CVD-IP) have been reported to be either reduced (25)(26)(27) or unchanged (28,29). Reduced or unchanged SP-A and SP-D levels in BALF from clinically stable patients with cystic fibrosis have also been reported, but increased levels have been found when the disease progressed as a result of infection (30,31). SP-A or SP-D levels in BALF of pulmonary sarcoidosis patients have been reported to be increased (7,32), unchanged (7), or reduced (27,29).…”

Increased and Prolonged Pulmonary Fibrosis in Surfactant Protein C-Deficient Mice Following Intratracheal Bleomycin

“…Supernatants were then analyzed for the four surfactant proteins, SP-A, SP-B, SP-C, and SP-D. Lavage content of SP-B and SP-D was measured by specific enzyme-linked immunosorbent assay (ELISA) as previously reported. [22][23][24] Western blots were performed for SP-A and the mature form of SP-C using polyclonal antibodies as previously described. 17 Densitometry was performed using Gelworks 1D Advanced V3.01 software (Ultra-Violet Products, Cambridge, UK) and the individual band density was normalized to a positive control run on each gel.…”

Immune Dysfunction in Cystic Fibrosis

“…Defensins Impaired activity Goldman MJ et al 1997, Bals R et al 2001 Surfactant proteins Decreased or inactive Hartl D, Griese M 2006, Meyer KC et al 2000, Noah TL et al 2003 Antioxidants Reduced glutathione availability in airways Gao L et al 1999, Roum JH et al 1993, Day BJ 2005, Childers M et al 2007 Moss RB et al1996, Mueller C et al2010 IL-6 4 Increased secretion Black HR et al 1998, Becker MN et al 2004, Andersson C et al 2007, Vandivier RW et al 2009 Increased secretion Bonfield TL et al 1995, Black HR et al 1998, Becker MN et al 2004, Vandivier RW et al 2009 Altered secretion Bonfield TL et al 1995, Moss RB et al 1996, Armstrong DS et al 2005 Increased secretion Mueller C et al2010 IL-17 8 Increased secretion McAllister F et al2005, Tan HL et al2011 TNF- 9 Increased secretion Bonfield TL et al 1995, Andersson C et al 2007 Increased secretion Brennan S et al 2009 MCP-1 11 Increased secretion Brennan S et al 2009 Notes: 1 IFN-( interferon-gamma); 2 IL-1(interleukin-1 beta), 3 IL-4 (interleukin-4), 4 IL-6 (interleukin-6), 5 IL-8 (interleukin-8), 6 IL-10 (interleukin-10), 7 IL-13 (interleukin-13), [8][9][10][11][12][13][14][15][16][17], 9 TNF-...…”