Abstract
Asthma is a major cause of morbidity and mortality worldwide and its prevalence is increasing. Increased airway smooth muscle (ASM) mass is a hallmark of asthma, which increases with disease severity and is associated with decline in lung function. Fibrocytes (FCs) are elevated in the peripheral blood and ASM in asthma and ASM has the potential to mediate FC recruitment (Saunders et al, J Allergy Clin Immunol, 2009;123:376-84). We hypothesised that once recruited to the ASM FCs differentiate into a more ASM like phenotype under the influence of local factors.
FCs were isolated from peripheral blood, ASM from bronchial biopsies and lung resection material. FCs were labelled with CFSE prior to culture with ASM cells for 7d, allowing identification by gating following flow cytometry.
24h after isolation from the peripheral blood cells are predominantly CD14high/α-smooth muscle actin (αSMA)low. Subsequent monoculture yields CD14low/αSMAhigh cells, consistent with differentiation to fibrocytes. Coculture with ASM from both non-asthmatic (NA) and asthmatic (A) donors yields CD14high FCs, whereas ASM from NA donors yields αSMAlow FCs and ASM from A donors yields αSMAhigh FCs (Table 1).
Our results show that FCs have the capability to undergo phenotypic plasticity, depending on culture conditions. Further work is required to understand the factors affecting FC differentiation upon localisation to the ASM in asthma and the resultant contribution of FCs to ASM dysfunction.
- © 2012 ERS