Biomedical Engineering Reference
In-Depth Information
Figure 6
Interactions between neutrophils and macrophages in COPD. 1. Cigarette
smoke activates epithelial cells, and macrophages and neutrophils once recruited into
the airways; 2. Epithelial cells, macrophages and neutrophils secrete cytokines (such
as TNF
a
and IL-1
b
) and chemokines (such as CXCL8), which recruit further leuko-
cyte entry into the lung; 3. Once recruited, macrophages secrete MMPs and cathepsin
B, which process neutrophil chemoattractants (such as MMP-12 acting on TNF-
a
)
enhancing neutrophil recruitment, and degrade matrix proteins. MMP and cathepsin
B also degrades neutrophil elastase (NE) inhibitors (
a
1AT and SLPI) enhancing NE
activity. 4. Neutrophils secrete NE, which leads to protein degradation. NE activates
macrophage Cathepsin B and MMPs, and degrades their primary inhibitors, Cysta-
tin C and TIMP (leading to further protein degradation, cytokine modulation and
neutrophil recruitment).
do not take us further in understanding the overlapping actions of all pro-
teinases in unison, and in depth studies of cells and chemoattractants in man
are awaited.
VII. CONCLUSIONS
There is strong evidence supporting the hypothesis that the neutrophil is
fundamental in the pathogenesis of COPD and only the neutrophil has been
shown to be able to cause all of the pathological changes of the disease
including emphysema, mucus hyper secretion, and reduced ciliary beating.
