Elevated complement factor H levels in asthmatic sputa

Z. Weiszhár; A. Bikov; G. Gálffy; L. Tamási; I. Ungvári; C. Szalai; G. Losonczy; I. Horváth

doi:10.1007/s10875-012-9807-8

Elevated complement factor H levels in asthmatic sputa

Z. Weiszhár, A. Bikov, G. Gálffy, L. Tamási, I. Ungvári, C. Szalai, G. Losonczy, I. Horváth

Division of Immunology, Immunity to Infection and Respiratory Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

Background: The alternative pathway of the complement system is known to play a role in the generation of asthmatic airway inflammation, but its regulatory complement protein, factor H has not been investigated in this disease. Purpose Our aim was to determine the local bronchial complement factor H (CFH) levels in asthma, and to investigate its relationship with complement activation, systemic CFH concentrations and clinical characteristics of patients. Methods: Induced sputum and plasma were collected from 21 healthy and 26 asthmatic subjects, and complement factor H and SC5b-9 concentrations were assessed by ELISA. Total protein concentrations were determined by biuret-reaction based microassay system from induced sputa. Results: CFH was detectable in 81 % of healthy and 100 % of asthmatic subjects, while SC5b-9 exceeded the detection limit in 62 % of healthy subjects and 85 % of asthmatic patients. Sputum CFH concentrations and CFH/protein ratios were increased in samples from asthmatic patients, and correlated with loss of lung function, asthma control, severity and medication intensity, but not with plasma CFH concentrations. Sputum CFH/protein ratios were in positive correlation also with sputum eosinophilic cell counts in asthma. SC5b-9 concentrations were not higher in the asthmatic sputa, although they correlated with sputum CFH concentrations. Conclusions: CFH level is elevated on asthmatic airway surface, and may be associated with uncontrolled inflammation in asthma.

Original language	English
Pages (from-to)	496-505
Number of pages	10
Journal	Journal of clinical immunology
Volume	33
Issue number	2
DOIs	https://doi.org/10.1007/s10875-012-9807-8
Publication status	Published - 2013

Keywords

Airway inflammation
Asthma control
Complement factor H
Induced sputum
Severe asthma
complement factor H
SC5b-9 protein
unclassified drug
adult
article
asthma
bronchus
clinical article
clinical feature
complement activation
complement blood level
controlled study
correlation analysis
disease control
disease severity
eosinophil count
female
human
limit of detection
lung function
male
priority journal
sputum
Adult
Asthma
Case-Control Studies
Complement Factor H
Complement Membrane Attack Complex
Female
Humans
Male
Middle Aged
Sputum

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s10875-012-9807-8

https://www.scopus.com/inward/record.uri?eid=2-s2.0-84878903443&doi=10.1007%2fs10875-012-9807-8&partnerID=40&md5=456e780810fc4f6f3020d96a75571014

Cite this

@article{c6ca5bc0887f4e2ea7cae353335307f0,

title = "Elevated complement factor H levels in asthmatic sputa",

abstract = "Background: The alternative pathway of the complement system is known to play a role in the generation of asthmatic airway inflammation, but its regulatory complement protein, factor H has not been investigated in this disease. Purpose Our aim was to determine the local bronchial complement factor H (CFH) levels in asthma, and to investigate its relationship with complement activation, systemic CFH concentrations and clinical characteristics of patients. Methods: Induced sputum and plasma were collected from 21 healthy and 26 asthmatic subjects, and complement factor H and SC5b-9 concentrations were assessed by ELISA. Total protein concentrations were determined by biuret-reaction based microassay system from induced sputa. Results: CFH was detectable in 81 % of healthy and 100 % of asthmatic subjects, while SC5b-9 exceeded the detection limit in 62 % of healthy subjects and 85 % of asthmatic patients. Sputum CFH concentrations and CFH/protein ratios were increased in samples from asthmatic patients, and correlated with loss of lung function, asthma control, severity and medication intensity, but not with plasma CFH concentrations. Sputum CFH/protein ratios were in positive correlation also with sputum eosinophilic cell counts in asthma. SC5b-9 concentrations were not higher in the asthmatic sputa, although they correlated with sputum CFH concentrations. Conclusions: CFH level is elevated on asthmatic airway surface, and may be associated with uncontrolled inflammation in asthma.",

keywords = "Airway inflammation, Asthma control, Complement factor H, Induced sputum, Severe asthma, complement factor H, SC5b-9 protein, unclassified drug, adult, article, asthma, bronchus, clinical article, clinical feature, complement activation, complement blood level, controlled study, correlation analysis, disease control, disease severity, eosinophil count, female, human, limit of detection, lung function, male, priority journal, sputum, Adult, Asthma, Case-Control Studies, Complement Factor H, Complement Membrane Attack Complex, Female, Humans, Male, Middle Aged, Sputum",

author = "Z. Weiszh{\'a}r and A. Bikov and G. G{\'a}lffy and L. Tam{\'a}si and I. Ungv{\'a}ri and C. Szalai and G. Losonczy and I. Horv{\'a}th",

note = "Cited By :5 Export Date: 20 February 2019 CODEN: JCIMD Correspondence Address: Horv{\'a}th, I.; Department of Pulmonology, Semmelweis University, Dios arok 1/C, 1125, Budapest, Hungary; email: [email protected] Chemicals/CAS: complement factor H, 80295-65-4; Complement Factor H, 80295-65-4; Complement Membrane Attack Complex; SC5b-9 protein complex Funding details: Nemzeti Kutat{\'a}si {\'e}s Technol{\'o}giai Hivatal, NKTH Funding details: Orsz{\'a}gos Tudom{\'a}nyos Kutat{\'a}si Alapprogramok, OTKA, K81941 Funding details: Orsz{\'a}gos Tudom{\'a}nyos Kutat{\'a}si Alapprogramok, OTKA, OTKA K68808 Funding details: Orsz{\'a}gos Tudom{\'a}nyos Kutat{\'a}si Alapprogramok, OTKA, K68808, Funding details: National Research Council of Science and Technology, NST, TECH_08-A1/2-2008-0120 Funding text 1: Acknowledgements This work was supported by the Hungarian Scientific Research Fund (OTKA K68808, K81941) and NKTH (National Research and Technology) TECH_08-A1/2-2008-0120. The authors declare that they have no conflict of interest. English was proof read by the translation services company Z&Z Orient Ltd. References: Jatakanon, A., Lim, S., Barnes, P.J., Changes in sputum eosinophils predict loss of asthma control (2000) Am J Respir Crit Care Med, 161, pp. 64-72; Hastie, A.T., Moore, W.C., Meyers, D.A., Vestal, P.L., Li, H., Peters, S.P., Bleecker, E.R., National heart, lung, and blood institute severe asthma research program. Analyses of asthma severity phenotypes and inflammatory proteins in subjects stratified by sputum granulocytes (2010) J Allergy Clin Immunol, 125, pp. 1028-1036; Bowser, C., Erstein, D.P., Silverberg, J.I., Nowakowski, M., Joks, R., Correlation of plasma complement split product levels with allergic respiratory disease activity and relation to allergen immunotherapy (2010) Ann Allergy Asthma Immunol, 104, pp. 42-49; Nakano, Y., Morita, S., Kawamoto, A., Suda, T., Chida, K., Nakamura, H., Elevated complement C3a in plasma from patients with severe acute asthma (2003) J Allergy Clin Immunol, 112, pp. 525-530; Marc, M.M., Korosec, P., Kosnik, M., Kern, I., Flezar, M., Suskovic, S., Sorli, J., Complement factors c3a, c4a, and c5a in chronic obstructive pulmonary disease and asthma (2004) Am J Respir Cell Mol Biol, 31, pp. 216-219; Krug, N., Tschernig, T., Erpenbeck, V.J., Hohlfeld, J.M., K{\"o}hl, J., Complement factors C3a and C5a are increased in bronchoalveolar lavage fluid after segmental allergen provocation in subjects with asthma (2001) Am J Respir Crit Care Med, 164, pp. 1841-1843; Taube, C., Thurman, J.M., Takeda, K., Joetham, A., Miyahara, N., Carroll, M.C., Dakhama, A., Gelfand, E.W., Factor B of the alternative complement pathway regulates development of airway hyperresponsiveness and inflammation (2006) Proc Natl Acad Sci USA, 103, pp. 8084-8089; J{\'o}zsi, M., Manuelian, T., Heinen, S., Oppermann, M., Zipfel, P.F., Attachment of the soluble complement regulator factor H to cell and tissue surfaces: Relevance for pathology (2004) Histol Histopathol, 19, pp. 251-258; Ferreira, V.P., Pangburn, M.K., Cort{\'e}s, C., Complement control protein factor H: The good, the bad, and the inadequate (2010) Mol Immunol, 47, pp. 2187-2197; Pio, R., Garcia, J., Corrales, L., Ajona, D., Fleischhacker, M., Pajares, M.J., Cardenal, F., Montuenga, L.M., Complement factor H is elevated in bronchoalveolar lavage fluid and sputum from patients with lung cancer (2010) Cancer Epidemiol Biomarkers Prev, 19, pp. 2665-2672; Spanevello, A., Migliori, G.B., Sharara, A., Ballardini, L., Bridge, P., Pisati, P., Neri, M., Ind, P.W., Induced sputum to assess airway inflammation: A study of reproducibility (1997) Clin Exp Allergy, 27, pp. 1138-1144; Spanevello, A., Confalonieri, M., Sulotto, F., Romano, F., Balzano, G., Migliori, G.B., Bianchi, A., Michetti, G., Induced sputum cellularity. Reference values and distribution in normal volunteers (2000) Am J Respir Crit Care Med, 162, pp. 1172-1174; Jayaram, L., Pizzichini, M.M., Cook, R.J., Boulet, L.P., Lemi{\`e}re, C., Pizzichini, E., Cartier, A., Hargreave, F.E., Determining asthma treatment by monitoring sputum cell counts: Effect on exacerbations (2006) Eur Respir J, 27, pp. 483-494; Malerba, M., Ragnoli, B., Radaeli, A., Tantucci, C., Usefulness of exhaled nitric oxide and sputum eosinophils nt he long-term control of eosinophilic asthma (2008) Chest, 134, pp. 733-739; Bakakos, P., Schleich, F., Alchanatis, M., Louis, R., Induced sputum in asthma: From bench to bedside (2011) Curr Med Chem, 18, pp. 1415-1422; (2011), http://www.ginasthma.org/, Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA); Dweik, R.A., Boggs, P.B., Erzurum, S.C., Irvin, C.G., Leigh, M.W., Lundberg, J.O., Olin, A.-C., Robin Taylor, D., An official ATS clinical practice guideline: Interpretation of exhaled nitric oxide levels (FENO) for clinical applications (2011) Am J Respir Crit Care Med, 184, pp. 602-615. , and on behalf of the American Thoracic Society Committee on Interpretation of Exhaled Nitric Oxide Levels (FENO) for Clinical Applications; Miller, M.R., Hankinson, J., Brusasco, V., Burgos, F., Casaburi, R., Coates, A., Crapo, R., Wanger, J., Standardisation of spirometry (2005) Eur Respir J, 26, pp. 319-338; Quanjer, P.H., Tammeling, G.J., Cotes, J.E., Pedersen, O.F., Peslin, R., Yernault, J.-C., Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society (1993) Eur Respir J, 6 (SUPPL. 16), pp. 5-40; Cataldo, D., Foidart, J.M., Lau, L., Bartsch, P., Djukanovic, R., Louis, R., Induced sputum: Comparison between isotonic and hypertonic saline solution inhalation in patients with asthma (2001) Chest, 120, pp. 1815-1821; Weiszh{\'a}r, Z., Cz{\'u}cz, J., R{\'e}v{\'e}sz, C., Rosivall, L., Szebeni, J., Rozsnyay, Z., Complement activation by polyethoxylated pharmaceutical surfactants: Cremophor-EL, Tween-80 and Tween-20 (2012) Eur J Pharm Sci, 45, pp. 492-498; Chung, K.F., Rogers, D.F., Barnes, P.J., Evans, T.W., The role of increased airway microvascular permeability and plasma exudation in asthma (1990) Eur Respir J, 3, pp. 329-337; Zanini, A., Chetta, A., Imperatori, A.S., Spanevello, A., Olivieri, D., The role of the bronchial microvasculature in the airway remodelling in asthma and COPD (2010) Respir Res, 11, p. 132; Strunk, R.C., Eidlen, D.M., Mason, R.J., Pulmonary alveolar type II epithelial cells synthesize and secrete proteins of the classical and alternative complement pathways (1988) J Clin Invest, 81, pp. 1419-1426; Morgan, B.P., Gasque, P., Extrahepatic complement biosynthesis: Where, when and why? (1997) Clin Exp Immunol, 107, pp. 1-7; Dave, S., Brooks-Walter, A., Pangburn, M.K., McDaniel, L.S., PspC, a pneumococcal surface protein, binds human factor H (2001) Infect Immun, 69, pp. 3435-3437; Hallstr{\"o}m, T., Zipfel, P.F., Blom, A.M., Lauer, N., Forsgren, A., Riesbeck, K., Haemophilus influenzae interacts with the human complement inhibitor factor H (2008) J Immunol, 181, pp. 537-545; Vogl, G., Lesiak, I., Jensen, D.B., Perkhofer, S., Eck, R., Speth, C., Lass-Florl, C., Wurzner, R., Immune evasion by acquisition of complement inhibitors: The mould Aspergillus binds both factor H and C4b binding protein (2008) Mol Immunol, 45, pp. 1485-1493; Zhang, N., Truong-Tran, Q.A., Tancowny, B., Harris, K.E., Schleimer, R.P., Glucocorticoids enhance or spare innate immunity: Effects in airway epithelium are mediated by CCAAT/enhancer binding proteins (2007) J Immunol, 179, pp. 578-589; Falus, A., Walcz, E., Brozik, M., Rokita, H., Fust, G., Hajnal, A., Meretey, K., Stimulation of histamine receptors of human monocytoid and hepatoma-derived cell lines and mouse hepatocytes modulates the production of the complement components C3, C4, factor B, and C2 (1989) Scand J Immunol, 30, pp. 241-248; Schleich, F.N., Seidel, L., Sele, J., Manise, M., Quaedvlieg, V., Michils, A., Louis, R., Exhaled nitric oxide thresholds associated with a sputum eosinophil count ≥3 % in a cohort of unselected patients with asthma (2010) Thorax, 65, pp. 1039-1044; Kew, R.R., Ghebrehiwet, B., Janoff, A., Cigarette smoke can activate the alternative pathway of complement in vitro by modifying the third component of complement (1985) J Clin Invest, 75, pp. 1000-1007; Malinovschi, A., Janson, C., Holmkvist, T., Norb{\"a}ck, D., Meril{\"a}inen, P., H{\"o}gman, M., Effect of smoking on exhaled nitric oxide and flowindependent nitric oxide exchange parameters (2006) Eur Respir J, 28, pp. 339-345; Chalmers, G.W., MacLeod, K.J., Thomson, L., Little, S.A., McSharry, C., Thomson, N.C., Smoking and airway inflammation in patients with mild asthma (2001) Chest, 120, pp. 1917-1922; Marc, M.M., Kristan, S.S., Rozman, A., Kern, I., Flezar, M., Kosnik, M., Korosec, P., Complement factor C5a in acute exacerbation of Chronic Obstructive Pulmonary Disease (2010) Scand J Immunol, 71, pp. 386-391; B{\'i}r{\'o}, A., Proh{\'a}szka, Z., F{\"u}st, G., Blask{\'o}, B., Determination of complement factor H functional polymorphisms (V62I, Y402H, and E936D) using sequence-specific primer PCR and restriction fragment length polymorphisms (2006) Mol Diagn Ther, 10, pp. 303-310",

year = "2013",

doi = "10.1007/s10875-012-9807-8",

language = "English",

volume = "33",

pages = "496--505",

journal = "Journal of clinical immunology",

issn = "0271-9142",

publisher = "Springer Nature",

number = "2",

}

TY - JOUR

T1 - Elevated complement factor H levels in asthmatic sputa

AU - Weiszhár, Z.

AU - Bikov, A.

AU - Gálffy, G.

AU - Tamási, L.

AU - Ungvári, I.

AU - Szalai, C.

AU - Losonczy, G.

AU - Horváth, I.

N1 - Cited By :5 Export Date: 20 February 2019 CODEN: JCIMD Correspondence Address: Horváth, I.; Department of Pulmonology, Semmelweis University, Dios arok 1/C, 1125, Budapest, Hungary; email: [email protected] Chemicals/CAS: complement factor H, 80295-65-4; Complement Factor H, 80295-65-4; Complement Membrane Attack Complex; SC5b-9 protein complex Funding details: Nemzeti Kutatási és Technológiai Hivatal, NKTH Funding details: Országos Tudományos Kutatási Alapprogramok, OTKA, K81941 Funding details: Országos Tudományos Kutatási Alapprogramok, OTKA, OTKA K68808 Funding details: Országos Tudományos Kutatási Alapprogramok, OTKA, K68808, Funding details: National Research Council of Science and Technology, NST, TECH_08-A1/2-2008-0120 Funding text 1: Acknowledgements This work was supported by the Hungarian Scientific Research Fund (OTKA K68808, K81941) and NKTH (National Research and Technology) TECH_08-A1/2-2008-0120. The authors declare that they have no conflict of interest. English was proof read by the translation services company Z&Z Orient Ltd. References: Jatakanon, A., Lim, S., Barnes, P.J., Changes in sputum eosinophils predict loss of asthma control (2000) Am J Respir Crit Care Med, 161, pp. 64-72; Hastie, A.T., Moore, W.C., Meyers, D.A., Vestal, P.L., Li, H., Peters, S.P., Bleecker, E.R., National heart, lung, and blood institute severe asthma research program. Analyses of asthma severity phenotypes and inflammatory proteins in subjects stratified by sputum granulocytes (2010) J Allergy Clin Immunol, 125, pp. 1028-1036; Bowser, C., Erstein, D.P., Silverberg, J.I., Nowakowski, M., Joks, R., Correlation of plasma complement split product levels with allergic respiratory disease activity and relation to allergen immunotherapy (2010) Ann Allergy Asthma Immunol, 104, pp. 42-49; Nakano, Y., Morita, S., Kawamoto, A., Suda, T., Chida, K., Nakamura, H., Elevated complement C3a in plasma from patients with severe acute asthma (2003) J Allergy Clin Immunol, 112, pp. 525-530; Marc, M.M., Korosec, P., Kosnik, M., Kern, I., Flezar, M., Suskovic, S., Sorli, J., Complement factors c3a, c4a, and c5a in chronic obstructive pulmonary disease and asthma (2004) Am J Respir Cell Mol Biol, 31, pp. 216-219; Krug, N., Tschernig, T., Erpenbeck, V.J., Hohlfeld, J.M., Köhl, J., Complement factors C3a and C5a are increased in bronchoalveolar lavage fluid after segmental allergen provocation in subjects with asthma (2001) Am J Respir Crit Care Med, 164, pp. 1841-1843; Taube, C., Thurman, J.M., Takeda, K., Joetham, A., Miyahara, N., Carroll, M.C., Dakhama, A., Gelfand, E.W., Factor B of the alternative complement pathway regulates development of airway hyperresponsiveness and inflammation (2006) Proc Natl Acad Sci USA, 103, pp. 8084-8089; Józsi, M., Manuelian, T., Heinen, S., Oppermann, M., Zipfel, P.F., Attachment of the soluble complement regulator factor H to cell and tissue surfaces: Relevance for pathology (2004) Histol Histopathol, 19, pp. 251-258; Ferreira, V.P., Pangburn, M.K., Cortés, C., Complement control protein factor H: The good, the bad, and the inadequate (2010) Mol Immunol, 47, pp. 2187-2197; Pio, R., Garcia, J., Corrales, L., Ajona, D., Fleischhacker, M., Pajares, M.J., Cardenal, F., Montuenga, L.M., Complement factor H is elevated in bronchoalveolar lavage fluid and sputum from patients with lung cancer (2010) Cancer Epidemiol Biomarkers Prev, 19, pp. 2665-2672; Spanevello, A., Migliori, G.B., Sharara, A., Ballardini, L., Bridge, P., Pisati, P., Neri, M., Ind, P.W., Induced sputum to assess airway inflammation: A study of reproducibility (1997) Clin Exp Allergy, 27, pp. 1138-1144; Spanevello, A., Confalonieri, M., Sulotto, F., Romano, F., Balzano, G., Migliori, G.B., Bianchi, A., Michetti, G., Induced sputum cellularity. Reference values and distribution in normal volunteers (2000) Am J Respir Crit Care Med, 162, pp. 1172-1174; Jayaram, L., Pizzichini, M.M., Cook, R.J., Boulet, L.P., Lemière, C., Pizzichini, E., Cartier, A., Hargreave, F.E., Determining asthma treatment by monitoring sputum cell counts: Effect on exacerbations (2006) Eur Respir J, 27, pp. 483-494; Malerba, M., Ragnoli, B., Radaeli, A., Tantucci, C., Usefulness of exhaled nitric oxide and sputum eosinophils nt he long-term control of eosinophilic asthma (2008) Chest, 134, pp. 733-739; Bakakos, P., Schleich, F., Alchanatis, M., Louis, R., Induced sputum in asthma: From bench to bedside (2011) Curr Med Chem, 18, pp. 1415-1422; (2011), http://www.ginasthma.org/, Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA); Dweik, R.A., Boggs, P.B., Erzurum, S.C., Irvin, C.G., Leigh, M.W., Lundberg, J.O., Olin, A.-C., Robin Taylor, D., An official ATS clinical practice guideline: Interpretation of exhaled nitric oxide levels (FENO) for clinical applications (2011) Am J Respir Crit Care Med, 184, pp. 602-615. , and on behalf of the American Thoracic Society Committee on Interpretation of Exhaled Nitric Oxide Levels (FENO) for Clinical Applications; Miller, M.R., Hankinson, J., Brusasco, V., Burgos, F., Casaburi, R., Coates, A., Crapo, R., Wanger, J., Standardisation of spirometry (2005) Eur Respir J, 26, pp. 319-338; Quanjer, P.H., Tammeling, G.J., Cotes, J.E., Pedersen, O.F., Peslin, R., Yernault, J.-C., Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society (1993) Eur Respir J, 6 (SUPPL. 16), pp. 5-40; Cataldo, D., Foidart, J.M., Lau, L., Bartsch, P., Djukanovic, R., Louis, R., Induced sputum: Comparison between isotonic and hypertonic saline solution inhalation in patients with asthma (2001) Chest, 120, pp. 1815-1821; Weiszhár, Z., Czúcz, J., Révész, C., Rosivall, L., Szebeni, J., Rozsnyay, Z., Complement activation by polyethoxylated pharmaceutical surfactants: Cremophor-EL, Tween-80 and Tween-20 (2012) Eur J Pharm Sci, 45, pp. 492-498; Chung, K.F., Rogers, D.F., Barnes, P.J., Evans, T.W., The role of increased airway microvascular permeability and plasma exudation in asthma (1990) Eur Respir J, 3, pp. 329-337; Zanini, A., Chetta, A., Imperatori, A.S., Spanevello, A., Olivieri, D., The role of the bronchial microvasculature in the airway remodelling in asthma and COPD (2010) Respir Res, 11, p. 132; Strunk, R.C., Eidlen, D.M., Mason, R.J., Pulmonary alveolar type II epithelial cells synthesize and secrete proteins of the classical and alternative complement pathways (1988) J Clin Invest, 81, pp. 1419-1426; Morgan, B.P., Gasque, P., Extrahepatic complement biosynthesis: Where, when and why? (1997) Clin Exp Immunol, 107, pp. 1-7; Dave, S., Brooks-Walter, A., Pangburn, M.K., McDaniel, L.S., PspC, a pneumococcal surface protein, binds human factor H (2001) Infect Immun, 69, pp. 3435-3437; Hallström, T., Zipfel, P.F., Blom, A.M., Lauer, N., Forsgren, A., Riesbeck, K., Haemophilus influenzae interacts with the human complement inhibitor factor H (2008) J Immunol, 181, pp. 537-545; Vogl, G., Lesiak, I., Jensen, D.B., Perkhofer, S., Eck, R., Speth, C., Lass-Florl, C., Wurzner, R., Immune evasion by acquisition of complement inhibitors: The mould Aspergillus binds both factor H and C4b binding protein (2008) Mol Immunol, 45, pp. 1485-1493; Zhang, N., Truong-Tran, Q.A., Tancowny, B., Harris, K.E., Schleimer, R.P., Glucocorticoids enhance or spare innate immunity: Effects in airway epithelium are mediated by CCAAT/enhancer binding proteins (2007) J Immunol, 179, pp. 578-589; Falus, A., Walcz, E., Brozik, M., Rokita, H., Fust, G., Hajnal, A., Meretey, K., Stimulation of histamine receptors of human monocytoid and hepatoma-derived cell lines and mouse hepatocytes modulates the production of the complement components C3, C4, factor B, and C2 (1989) Scand J Immunol, 30, pp. 241-248; Schleich, F.N., Seidel, L., Sele, J., Manise, M., Quaedvlieg, V., Michils, A., Louis, R., Exhaled nitric oxide thresholds associated with a sputum eosinophil count ≥3 % in a cohort of unselected patients with asthma (2010) Thorax, 65, pp. 1039-1044; Kew, R.R., Ghebrehiwet, B., Janoff, A., Cigarette smoke can activate the alternative pathway of complement in vitro by modifying the third component of complement (1985) J Clin Invest, 75, pp. 1000-1007; Malinovschi, A., Janson, C., Holmkvist, T., Norbäck, D., Meriläinen, P., Högman, M., Effect of smoking on exhaled nitric oxide and flowindependent nitric oxide exchange parameters (2006) Eur Respir J, 28, pp. 339-345; Chalmers, G.W., MacLeod, K.J., Thomson, L., Little, S.A., McSharry, C., Thomson, N.C., Smoking and airway inflammation in patients with mild asthma (2001) Chest, 120, pp. 1917-1922; Marc, M.M., Kristan, S.S., Rozman, A., Kern, I., Flezar, M., Kosnik, M., Korosec, P., Complement factor C5a in acute exacerbation of Chronic Obstructive Pulmonary Disease (2010) Scand J Immunol, 71, pp. 386-391; Bíró, A., Prohászka, Z., Füst, G., Blaskó, B., Determination of complement factor H functional polymorphisms (V62I, Y402H, and E936D) using sequence-specific primer PCR and restriction fragment length polymorphisms (2006) Mol Diagn Ther, 10, pp. 303-310

PY - 2013

Y1 - 2013

N2 - Background: The alternative pathway of the complement system is known to play a role in the generation of asthmatic airway inflammation, but its regulatory complement protein, factor H has not been investigated in this disease. Purpose Our aim was to determine the local bronchial complement factor H (CFH) levels in asthma, and to investigate its relationship with complement activation, systemic CFH concentrations and clinical characteristics of patients. Methods: Induced sputum and plasma were collected from 21 healthy and 26 asthmatic subjects, and complement factor H and SC5b-9 concentrations were assessed by ELISA. Total protein concentrations were determined by biuret-reaction based microassay system from induced sputa. Results: CFH was detectable in 81 % of healthy and 100 % of asthmatic subjects, while SC5b-9 exceeded the detection limit in 62 % of healthy subjects and 85 % of asthmatic patients. Sputum CFH concentrations and CFH/protein ratios were increased in samples from asthmatic patients, and correlated with loss of lung function, asthma control, severity and medication intensity, but not with plasma CFH concentrations. Sputum CFH/protein ratios were in positive correlation also with sputum eosinophilic cell counts in asthma. SC5b-9 concentrations were not higher in the asthmatic sputa, although they correlated with sputum CFH concentrations. Conclusions: CFH level is elevated on asthmatic airway surface, and may be associated with uncontrolled inflammation in asthma.

AB - Background: The alternative pathway of the complement system is known to play a role in the generation of asthmatic airway inflammation, but its regulatory complement protein, factor H has not been investigated in this disease. Purpose Our aim was to determine the local bronchial complement factor H (CFH) levels in asthma, and to investigate its relationship with complement activation, systemic CFH concentrations and clinical characteristics of patients. Methods: Induced sputum and plasma were collected from 21 healthy and 26 asthmatic subjects, and complement factor H and SC5b-9 concentrations were assessed by ELISA. Total protein concentrations were determined by biuret-reaction based microassay system from induced sputa. Results: CFH was detectable in 81 % of healthy and 100 % of asthmatic subjects, while SC5b-9 exceeded the detection limit in 62 % of healthy subjects and 85 % of asthmatic patients. Sputum CFH concentrations and CFH/protein ratios were increased in samples from asthmatic patients, and correlated with loss of lung function, asthma control, severity and medication intensity, but not with plasma CFH concentrations. Sputum CFH/protein ratios were in positive correlation also with sputum eosinophilic cell counts in asthma. SC5b-9 concentrations were not higher in the asthmatic sputa, although they correlated with sputum CFH concentrations. Conclusions: CFH level is elevated on asthmatic airway surface, and may be associated with uncontrolled inflammation in asthma.

KW - Airway inflammation

KW - Asthma control

KW - Complement factor H

KW - Induced sputum

KW - Severe asthma

KW - complement factor H

KW - SC5b-9 protein

KW - unclassified drug

KW - adult

KW - article

KW - asthma

KW - bronchus

KW - clinical article

KW - clinical feature

KW - complement activation

KW - complement blood level

KW - controlled study

KW - correlation analysis

KW - disease control

KW - disease severity

KW - eosinophil count

KW - female

KW - human

KW - limit of detection

KW - lung function

KW - male

KW - priority journal

KW - sputum

KW - Adult

KW - Asthma

KW - Case-Control Studies

KW - Complement Factor H

KW - Complement Membrane Attack Complex

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Sputum

U2 - 10.1007/s10875-012-9807-8

DO - 10.1007/s10875-012-9807-8

M3 - Article

SN - 0271-9142

VL - 33

SP - 496

EP - 505

JO - Journal of clinical immunology

JF - Journal of clinical immunology

IS - 2

ER -

Elevated complement factor H levels in asthmatic sputa

Abstract

Keywords

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