Specific Haptoglobin Expression in Bronchoalveolar Lavage during Differentiation of Circulating Fibroblast Progenitor Cells in Mild Asthma

Abstract

Haptoglobin is an acute-phase glycoprotein considered to be involved in tissue repair and is produced by fibroblasts and inflammatory cells. By using a gel-based proteomic approach, we show for the first time a possible role for haptoglobin in the differentiation of fibroblast progenitor cells, termed fibrocytes, in patients with mild asthma. Bronchoalveolar lavage fluid (BALF) was performed to sample circulating fibrocytes from patients with mild asthma and nonasthmatic control subjects. Fibrocytes from the airway lumen were characterized by triple staining of the markers CD34/CD45R0/alpha-smooth muscle actin, and subjected to confocal microscopy. The protein expression pattern was analyzed using two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF). Elevated levels of haptoglobin expression in BALF was reported in a sub-group of patients with mild asthma (p < 0.05) when compared to the other subjects. In addition, this increase in haptoglobin was accompanied by differentiation of fibrocytes into fibroblast-like cells. When further analyzing the expression pattern of haptoglobin isoforms, a heterozygous expression was detected in the patients where fibrocyte differentiation could be observed. These data raise the possibility that an acute and specific inflammatory state facilitates the differentiation of fibroblast progenitor cells into activated fibroblasts. Furthermore, this study proposes a novel role for haptoglobin in airway remodeling in patients with asthma.

Inhibitory effect of CXC chemokine receptor 4 antagonist AMD3100 on bleomycin induced murine pulmonary fibrosis

“…On the basis of the expression of CD34 by fibrocytes (Bucala et al, 1994;Abe et al, 2001), the presence of CD34+ cells that also express COL I and α-smooth muscle actin in the bronchial mucosa of patients with allergic asthma (Schmidt et al, 2003) suggests that circulating fibrocytes are potential precursors for the fibroblast/myofibroblast in the remodeling airway wall. The mechanism by which fibrocytes are induced to undergo phenotypic transformation into fibroblasts and myofibroblasts and contribute of fibrogenesis in lung are poorly understood, although recently both haptoglobin and cysteinyl leukotrienes have been implicated (Larsen et al, 2006;Vannella et al, 2007). CXCR4 is a G protein-linked seven transmemtrane spanning receptor that was first identified as a co-factor for T cell-tropic HIV-1 and -2 viral entry into cells (Feng et al, 1996).…”

Oxidative Stress and Asthma: Proteome Analysis of Chitinase-like Proteins and FIZZ1 in Lung Tissue and Bronchoalveolar Lavage Fluid

“…Haptoglobin is an acute-phase glycoprotein considered to be involved in tissue repair and is produced by fibroblasts and inflammatory cells. An elevated level of haptoglobin expression in BALF was reported from patients with mild asthma as compared to the other healthy subjects 30. One of the major functions of haptoglobin is to bind to hemoglobin and thereby prevent the oxidative tissue damage mediated by free hemoglobin 32…”

Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) – an Introduction for Biologists

“…It seems that an ongoing damage is occurring in lung of these patients. A recent proteomic study has also shown that levels of haptoglobin are elevated in BAL fluid in patients with mild asthma, and reported that haptoglobin may play a role in the differentiation of fibroblast progenitor cells, suggesting a novel role for haptoglobin in airway remodeling in patients with asthma [20]. Conversely Nishioka et al showed that the serum concentration of haptoglobin was decreased during acute exacerbation in asthmatic children [21].…”