Tissue fibrocytes in patients with mild asthma: a possible link to thickness of reticular basement membrane?
BACKGROUND
Myofibroblasts, proposed as being derived from circulating fibrocytes, are considered to be important cells in thickening of the basement membrane in patients with asthma. We have studied the correlation of tissue fibrocyte levels to basement membrane thickness and the presence of fibrocytes in bronchoalveolar lavage fluid (BALF) in steroid-naive patients with mild asthma and controls.


METHODS
Patients with mild asthma (n = 9) were recruited and divided into two categories based on whether or not fibroblast-like cells could be established from BALF. Non-asthmatic healthy subjects (n = 5) were used as controls. Colocalization of the fibrocyte markers CD34, CD45RO, procollagen I, and alpha-smooth muscle actin (alpha-SMA) were identified in bronchial biopsies from patients and controls by confocal microscopy. Kruskall-Wallis method was used to calculate statistical significance and Spearman coefficient of rank correlation was used to assess the degree of association.


RESULTS
In patients with BALF fibroblasts, a 14-fold increase of tissue cells expressing CD34/CD45RO/alpha-SMA and a 16-fold increase of tissue cells expressing CD34/procollagen I was observed when compared to controls (p < 0.05). In contrast, patients without BALF fibroblasts displayed a 2-fold increase when compared to controls (p < 0.05). Fibrocytes were localized close to the basement membrane which was significantly thicker in patients with BALF fibroblasts when compared to the other two groups of subjects. Furthermore, basement membrane thickness could be correlated to the number of fibrocytes in tissue (r = 0.711). Fibroblasts-like cells were cultured from BALF where 17.6% of these cells expressed CD34, CD45RO and alpha-SMA.


CONCLUSIONS
These findings indicate a correlation between recruited fibrocytes in tissue and thickness of basement membrane. Fibroblast progenitor cells may therefore be important in airway remodeling in steroid-naive patients with mild asthma.
Department of Experimental Medical Science, Lund University BMC C13, S-221 84 Lund, Sweden. kristian.nihlberg@med.lu.se
Kristian
K
Nihlberg
Kristoffer
K
Larsen
Anna
A
Hultgårdh-Nilsson
Anders
A
Malmström
Leif
L
Bjermer
Gunilla
G
Westergren-Thorsson
D000328:Adult; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D001485:Basement Membrane / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D015415:Biomarkers / Q000032:analysis; D001980:Bronchi / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008875:Middle Aged; D012157:Mononuclear Phagocyte System / Q000276:immunology / Q000378:metabolism / Q000473:pathology*
D015415:Biomarkers