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CLC number: R562.2+5

On-line Access: 2015-08-04

Received: 2015-05-26

Revision Accepted: 2015-07-25

Crosschecked: 2015-07-08

Cited: 1

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Citations:  Bibtex RefMan EndNote GB/T7714


Sabrina Mattoli


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Journal of Zhejiang University SCIENCE B 2015 Vol.16 No.8 P.651-660


Pathogenetic and prognostic roles of bloodborne fibrocytes in asthma

Author(s):  Sabrina Mattoli

Affiliation(s):  Scientific Direction and Project Management, Avail Biomedical Research Institute, Postfach 102, CH-4010 Basel, Switzerland

Corresponding email(s):   smattoli@avail-research.com

Key Words:  Airway remodeling, Asthma, Biomarker, Chronic inflammation, Fibrocyte

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Sabrina Mattoli. Pathogenetic and prognostic roles of bloodborne fibrocytes in asthma[J]. Journal of Zhejiang University Science B, 2015, 16(8): 651-660.

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Bloodborne fibrocytes are cells mobilized from the bone marrow, which express surface antigens commonly ascribed to hematopoietic progenitors and have phenotypic and functional characteristics similar to those of immature mesenchymal cells. They exhibit predominant proinflammatory or profibrotic activities at tissue sites, depending on the host’s response to environmental insults and on the characteristics of the cell infiltrate and cytokine milieu. In patients with allergic asthma, fibrocytes egress from the bone marrow and are recruited into the airways after every allergen exposure and during viral infections. Recruited fibrocytes amplify the inflammatory responses driven by T helper type 2 lymphokines and favor viral replication and further inflammation on respiratory virus infections. Persistently elevated blood fibrocyte counts and persisting airway fibrocytosis are present in patients with chronically undertreated or corticosteroid-insensitive asthma, and are linked to an enhanced risk of adverse outcomes because of the major involvement of fibrocytes in the development of structural abnormalities that lead to chronic airflow obstruction in these patients. Consequently, blood fibrocyte count is an emerging biomarker of asthma control and disease progression and its clinical applicability as a new outcome measure deserves further evaluation in large clinical trials.


概要:血源性成纤维细胞来自骨髓,可表达一些通常造血祖细胞属性的表面抗原,同时有和未成熟间质细胞相似的表型和功能特征。依据机体对环境刺激的反应和局部浸润的细胞类型及不同的细胞因子环境,血源性成纤维细胞可局部组织显示强烈的促炎症活性或促纤维化活性。过敏性哮喘患者每次遭受过敏原暴露或病毒感染时,成纤维细胞即从骨髓中迁出并被募集至气道组织;而募集的成纤维细胞可放大由Th2细胞因子驱使的炎症反应,并有利于病毒的复制,进一步加重病毒感染引发的炎症。 在未治疗的慢性哮喘和激素不敏感的哮喘患者中可观察到持续性外周血成纤维细胞计数升高及气道纤维细胞浸润,而这和不良预后的风险增加有关。究其原因,成纤维细胞主要涉及气道结构异常的进展,而后者导致患者慢性气流受限。因此,外周血成纤维细胞计数是一种新发现的哮喘控制和疾病预后的生物学标记,作为一种新的结果检测方法,它的临床应用还需要大样本临床研究去评估。


Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Abe, R., Donnelly, S.C., Peng, T., et al., 2001. Peripheral blood fibrocytes: differentiation pathway and migration to wound sites. J. Immunol., 166(12):7556-7562.

[2]Bai, T.R., 2010. Evidence for airway remodeling in chronic asthma. Curr. Opin. Allergy Clin. Immunol., 10(1):82-86.

[3]Bellini, A., Marini, M.A., Bianchetti, L., et al., 2012. Interleukin (IL)-4, IL-13, and IL-17A differentially affect the profibrotic and proinflammatory functions of fibrocytes from asthmatic patients. Mucosal Immunol., 5(2):140-149.

[4]Bellini, A., Schmidt, M., Mattoli, S., 2013. Interactions between the bronchial epithelium and fibrocytes in the pathogenesis of airway remodeling in asthma. J. Epithelial Biol. Pharmacol., 6(1):1-10.

[5]Bianchetti, L., Marini, M.A., Isgrò, M., et al., 2012a. IL-33 promotes the migration and proliferation of circulating fibrocytes from allergen-exacerbated asthma. Biochem. Biophys. Res. Commun., 426(1):116-121.

[6]Bianchetti, L., Barczyk, M., Cardoso, J., et al., 2012b. Extracellular matrix remodelling properties of human fibrocytes. J. Cell. Mol. Med., 16(3):483-495.

[7]Bianchetti, L., Isgrò, M., Marini, M.A., et al., 2014. Enumeration of circulating fibrocytes for clinical use in asthma by an optimized single-platform flow cytometry assay. BBA Clin., 1:52-58.

[8]Bucala, R., Spiegel, L.A., Chesney, J., et al., 1994. Circulating fibrocytes define a new leukocyte subpopulation that mediates tissue repair. Mol. Med., 1(1):71-81.

[9]Chesney, J., Bacher, M., Bender, A., et al., 1997. The peripheral blood fibrocyte is a potent antigen-presenting cell capable of priming naive T cells in situ. PNAS, 94(12):6307-6312.

[10]Chesney, J., Metz, C., Stavitsky, A.B., et al., 1998. Regulated production of type I collagen and inflammatory cytokines by peripheral blood fibrocytes. J. Immunol., 160(1):419-425.

[11]Dorman, S.C., Babirad, I., Post, J., et al., 2005. Progenitor egress from the bone marrow after allergen challenge: role of stromal cell-derived factor 1α and eotaxin. J. Allergy Clin. Immunol., 115(3):501-507.

[12]Durrani, S.R., Viswanathan, R.K., Busse, W.W., 2011. What effect does asthma treatment have on airway remodeling? Current perspectives. J. Allergy Clin. Immunol., 128(3):439-448.

[13]Friedlander, S.L., Busse, W.W., 2005. The role of rhinovirus in asthma exacerbations. J. Allergy Clin. Immunol., 116(2):267-273.

[14]Global Initiative for Asthma, 2015. Global Strategy for Asthma Management and Prevention. Available from http://www.ginasthma.org/local/uploads/files/GINA_Report_2015_May19.pdf [Accessed on 26 May 2015].

[15]Guilbert, T.W., Morgan, W.J., Zeiger, R.S., et al., 2006. Long-term inhaled corticosteroids in preschool children at high risk for asthma. N. Engl. J. Med., 354(19):1985-1997.

[16]Halwani, R., Al-Muhsen, S., Hamid, Q., 2010. Airway remodeling in asthma. Curr. Opin. Pharmacol., 10(3):236-245.

[17]Holgate, S.T., 2008. Pathogenesis of asthma. Clin. Exp. Allergy, 38(6):872-897.

[18]Huang, C., Liu, W., Hu, Y., et al., 2015. Updated prevalence of asthma, allergy, and airway symptoms, a systematic review of trends over time for childhood asthma in Shanghai, China. PLoS ONE, 10(4):e0121577.

[19]Huang, J., Olivenstein, R., Taha, R., et al., 1999. Enhanced proteoglycan deposition in the airway wall of atopic asthmatics. Am. J. Respir. Crit. Care Med., 160(2):725-729.

[20]Isgrò, M., Bianchetti, L., Marini, M.A., et al., 2013a. Involvement of fibrocytes in allergen-induced T cell responses and rhinovirus infections in asthma. Biochem. Biophys. Res. Commun., 437(3):446-451.

[21]Isgrò, M., Bianchetti, L., Marini, M.A., et al., 2013b. The C-C motif chemokine ligands CCL5, CCL11, and CCL24 induce the migration of circulating fibrocytes from patients with severe asthma. Mucosal Immunol., 6(4):718-727.

[22]Jeffery, P.K., 2004. Remodeling and inflammation of bronchi in asthma and chronic obstructive pulmonary disease. Proc. Am. Thorac. Soc., 1(3):176-183.

[23]Khetsuriani, N., Kazerouni, N.N., Erdman, D.D., et al., 2007. Prevalence of viral respiratory tract infections in children with asthma. J. Allergy Clin. Immunol., 119(2):314-321.

[24]Martinez, D.M., 2011. New insights into the natural history of asthma: primary prevention on the horizon. J. Allergy Clin. Immunol., 128(5):939-945.

[25]Mattoli, S., 2006. Tissue repair in asthma: the origin of subepithelial fibroblasts and myofibroblasts. In: Chaponnier, C., Desmoulière, A., Gabbiani, G. (Eds.), Tissue Repair, Contraction and the Myofibroblasts. Landes Bioscience and Springer Science+Business Media, Georgetown, TX, p.40-46.

[26]Mattoli, S., 2015. Involvement of fibrocytes in asthma and clinical implications. Clin. Exp. Allergy, in press.

[27]Mori, L., Bellini, A., Stacey, M.A., et al., 2005. Fibrocytes contribute to the myofibroblast population in the wounded skin and originate from the bone marrow. Exp. Cell Res., 304(1):81-90.

[28]Muñoz-Fernández, R., Blanco, F.J., Frecha, C., et al., 2006. Follicular dendritic cells are related to bone marrow stromal cell progenitors and to myofibroblasts. J. Immunol., 177(1):280-289.

[29]Murray, C.S., Simpson, A., Custovic, A., 2004. Allergens, viruses, and asthma exacerbations. Proc. Am. Thorac. Soc., 1(2):99-104.

[30]National Asthma Education and Prevention Program, 2007. Expert Panel Report 3 (EPR-3): guidelines for the diagnosis and management of asthma—summary report 2007. J. Allergy Clin. Immunol., 120(5 Suppl.):S94-S138.

[31]Nihlberg, K., Larsen, K., Hultgårdh-Nilsson, A., et al., 2006. Tissue fibrocytes in patients with mild asthma: a possible link to thickness of reticular basement membrane? Respir. Res., 7:50.

[32]Olin, J.T., Wechsler, M.E., 2014. Asthma: pathogenesis and novel drugs for treatment. BMJ, 349:g5517

[33]Pascual, R.M., Peters, S.P., 2009. The irreversible component of persistent asthma. J. Allergy Clin. Immunol., 124(5):883-890.

[34]Pearce, N., Aït-Khaled, N., Beasley, R., et al., 2007. Worldwide trends in the prevalence of asthma symptoms: Phase III of the International Study of Asthma and Allergies in Childhood (ISAAC). Thorax, 62(9):758-766.

[35]Pini, L., Hamid, Q., Shannon, J., et al., 2007. Differences in proteoglycans deposition in the airways of moderate and severe asthmatics. Eur. Respir. J., 29(1):71-77.

[36]Reddel, H.K., Taylor, D.R., Bateman, E.D., et al., 2009. An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations. Standardizing endpoints for clinical asthma trials and clinical practice. Am. J. Respir. Crit. Care Med., 180(1):59-99.

[37]Roberts, C.R., 1995. Is asthma a fibrotic disease? Chest, 107 (3 Suppl.):111S-117S.

[38]Royce, S.G., Tang, M.L., 2009. The effects of current therapies on airway remodeling in asthma and new possibilities for treatment and prevention. Curr. Mol. Pharmacol., 2(2):169-181.

[39]Saada, J.I., Pinchuk, I.V., Barrera, C.A., et al., 2006. Subepithelial myofibroblasts are novel nonprofessional APCs in the human colonic mucosa. J. Immunol., 177(9):5968-5979.

[40]Saunders, R., Siddiqui, S., Kaur, D., et al., 2009. Fibrocyte localization to the airway smooth muscle is a feature of asthma. J. Allergy Clin. Immunol., 123(2):376-384.

[41]Sazuka, S., Katsumo, T., Nakagawa, T., et al., 2014. Fibrocytes are involved in inflammation as well as fibrosis in the pathogenesis of Crohn’s disease. Dig. Dis. Sci., 59(4):760-768.

[42]Schmidt, M., Mattoli, S., 2013. A mouse model for evaluating the contribution of fibrocytes and myofibroblasts to airway remodelling in allergic asthma. Methods Mol. Biol., 1032:235-255.

[43]Schmidt, M., Sun, G., Stacey, M.A., et al., 2003. Identification of circulating fibrocytes as precursors of bronchial myofibroblasts in asthma. J. Immunol., 171(1):380-389.

[44]Sehmi, R., Dorman, S., Baatjes, A., et al., 2003. Allergen-induced fluctuation in CC chemokine receptor 3 expression on bone marrow CD34+ cells from asthmatic subjects: significance for mobilization of haemopoietic progenitor cells in allergic inflammation. Immunology, 109(4):536-546.

[45]Singh, S.R., Sutcliffe, A., Kaur, D., et al., 2014. CCL2 release by airway smooth muscle is increased in asthma and promotes fibrocyte migration. Allergy, 69(9):1189-1197.

[46]Suga, H., Rennert, R.C., Rodrigues, M., et al., 2014. Tracking the elusive fibrocyte: identification and characterization of collagen-producing hematopoietic lineage cells during murine wound healing. Stem Cells, 32(5):1347-1360.

[47]Szefler, S.J., Wenzel, S., Brown, R., et al., 2012. Asthma outcomes: biomarkers. J. Allergy Clin. Immunol., 129(3):S9-S23.

[48]To, T., Stanojevic, S., Moores, G., et al., 2012. Global asthma prevalence in adults: findings from the cross-sectional world health survey. BMC Public Health, 12(1):204.

[49]Wang, C.H., Huang, C.D., Lin, H.C., et al., 2008. Increased circulating fibrocytes in asthma with chronic airflow obstruction. Am. J. Respir. Crit. Care Med., 178(6):583-591.

[50]Wang, C.H., Punde, T.H., Huang, C.D., et al., 2015. Fibrocyte trafficking in patients with chronic obstructive asthma and during an acute asthma exacerbation. J. Allergy Clin. Immunol., 135(5):1154-1162.e5.

[51]Zhang, W., Chen, X., Ma, L., et al., 2014. Epidemiology of bronchial asthma and asthma control assessment in Henan Province, China. Transl. Respir. Med., 2(1):5.

[52]Zhang, Y.P., Li, B.Z., Huang, C., et al., 2013. Ten cities cross-sectional questionnaire survey of children asthma and other allergies in China. Chin. Sci. Bull., 58(34):4182-4189.

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