Abstract
Chronic Obstructive Pulmonary Disease (COPD) is a common lung disease characterized by breathing difficulty as a consequence of narrowed airways. Previous studies have shown that COPD is correlated with neutrophil infiltration into the airways through chemotactic migration. However, whether neutrophil chemotaxis can be used to characterize and diagnose COPD is not well established. In the present study, we developed a microfluidic platform for evaluating neutrophil chemotaxis to sputum samples from COPD patients. Our results show increased neutrophil chemotaxis to COPD sputum compared to control sputum from healthy individuals. The level of COPD sputum induced neutrophil chemotaxis was correlated with the patient’s spirometry data. The cell morphology of neutrophils in a COPD sputum gradient is similar to the morphology displayed by neutrophils exposed to an IL-8 gradient, but not a fMLP gradient. In competing gradients of COPD sputum and fMLP, neutrophils chemotaxis and cell morphology are dominated by fMLP.
Highlights
Neutrophils are the ‘first responders’ to the site of inflammation and play important roles in the human innate immune system [1]
Our results showed that single Chronic Obstructive Pulmonary Disease (COPD) sputum gradients and single healthy control sputum gradients induced strong neutrophil chemotaxis as measured by the C.I. (Fig 3A)
The migration speed is comparable (Fig 3A). These results suggest that neutrophil chemotaxis to a sputum gradient measured in our microfluidic device can distinguish COPD patients and healthy control subjects
Summary
Neutrophils are the ‘first responders’ to the site of inflammation and play important roles in the human innate immune system [1]. Previous neutrophil chemotaxis studies in COPD were based on traditional cell migration assays, such as the transwell assay and the under-agarose assay [20, 22] Variations among these cell migration assays, and their common limitation in gradient control, has made it difficult to obtain reliable chemotaxis measurements, and in some cases has lead to contradictory results [21, 23]. Clinical factors such as the patient’s medical history and condition, methods of sample acquisition and processing, and the choice of control reference further complicate the interpretation of the chemotaxis results. We employed this system to assess the potential of neutrophil chemotaxis as a new clinical measure for COPD that may enable future point-of-care applications
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