iNOS and arginase expressing macrophages in COPD, nitrotyrosine (product of peroxynitrite) levels have been shown to be increased in sputum macrophages of COPD patients, which are negatively correlated with their lung function. Hence, the proportion of iNOS expressing M1 macrophages and arginase expressing M2 macrophages are really important to the oxidative/nitrosative environment of the lung (Vlahos and Bozinovski, 2014).
There are polarization states in between associated equilibriums that could significantly effect COPD progression. To back this up, there is significant evidence showing positive results on reprogramming alveolar macrophages that have been in contact with chronic smoke showing correlations with processes within a particular set of genes inclusive of a gene known as MMP12.
Added evidence can be found for transcriptional skewing within alveolar macrophages aimed at the M2 gene profile present in smokers having a normal functioning lung that is apparent in those smokers showing a progressive development to COPD. Studies done have also provided demonstrations on the progressive down regulation of the M1 gene.
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This may seem paradoxical towards increased expressions being observed in pro-inflammatory mediators within COPD. Because of this, we can conclude that there is a certainty of urgency when it comes to better defining significant contributions of the M1 and M2 macrophages due to there being evidence being developed sowing that both populations for sure exits in COPD airways.
An equally critical consideration in COPD is one that observed in the interaction seen between macrophages and T cell subsets. There are speculations stating that T cells are indeed the cells in control of the polarization state within macrophages. What must be made clear is that macrophages also contain a relative T cell biology; this is because T cell subsets includes CD8+ T cells, iBalt and TH17 formation that are present in COPD pathology. These macrophages have the job of regulating T cells biology remains being cleared up (Vlahos and Bozinovski, 2014).
When M2 skewed airway macrophages are accumulated, it is thought to be impaired resolution processes that normally would turn off inflammation and renew lung homeostasis. Non-phlogistric phagocytosis stimulation is crucial when it comes to the resolving of inflammation, the oxidant-dependent impairment of efferocytic clearance of damaged tissue may provide maintenance function in M2 macrophages with persons with COPD.
With the introduction of CD163 which is generally known as a marker for M2-alternatively activated macrophages that are involved in wound-healing, CD163 positive macrophages are most present in the BAL area of current and ex-smokers with COPD. CD163 has the capability of mounting a chief defence mechanism to protect the lung due to it functioning as a scavenger receptor; this in turn promotes degradation of HbHp complexes and signalling that activate expression of heme-oxygenase-1 (HO-1).
The tenacity of HO-1 in COPD airways is in accordance with an environment where there are great amounts of oxidative stress and a deficiency in the resolution of inflammation. The mediators that induce expression of M2 markers in COPD have not been comprehensively characterized.
Interleukin-10 (IL-10) is a potent inducer of CD163 expression in human monocytes; however, there is also data available that indicates that the level of IL-10 positive macrophages is reduced in COPD. There is an alternate mediator that been tested and proved to potently induces expressions of CD163 within human monocyte-derived macrophages, and is known as serum amyloid A (SAA).
SAA is a main acute phase reactant that only now have been found to show promise in COPD lungs, where its level correspond with neutrophilic inflammation. SAA is known to target the ALX/FPR2 receptor and oppose the actions of pro-resolving ligands such as LipoxinA4, which normally stimulate non-phlogistic clearance pathways.
Additionally with respect to CD163, SAA also possess the ability to stimulate the expression of the TH17 polarizing cytokines, IL-6, and IL-1β in monocyte-derived macrophages, and neutralization of IL-17A expression suppressed neutrophil airway inflammation stimulated by SAA. Thus, the tenacity of host defence mediators such as SAA have the ability to continue alternative macrophage populations in COPD airways that not only express M2 markers of wound repair, but also markers of acute inflammation (Vlahos and Bozinovski, 2014).
It is worth mentioning that oxidative stress, cigarette smoke and airway inflammatory microenvironment all show a direct effect on alveolar macrophages phenotype in COPD that shows an increase in M1 and M2 population. COPD pathology process is conducted by a ratio of, macrophages that are found in the inflamed environment. Macrophages that are known as M1 macrophages can move along the oxidative stress and inflammatory process.
Also, excessive oxidative is known to have negative effects on resolution mechanisms that includes macrophage mediated phagocytosis and efferocytosis. This leads to colonization and exacerbation within patients suffering from COPD. Thus, with the emergence of M2 macrophages, they can help to deleterious lung damage by the increase and expression of M2 related genes and also with excessive protease production of MMP-9 and 12 markers (Vlahos and Bozinovski, 2014).
With all the studies that have been concluded, there is now evidence to conclude that macrophages present in patients with COPD not only show an increase in numbers, but there is also a difference in their function when they are compared to healthy persons or smokers with normal lung function.
Thus, it should be noted that elevated expressions of proinflammatory mediators and effector molecules are both characteristic in COPD patients and are closely followed by a decrease in phagocytosis within respiratory pathogens and apoptotic cells. The mechanisms mentioned above may have a direct relationship in the inflammation and tissue injury that can be observed in patients with COPD.
Alveolar macrophages conduct the task of coordinating efficiently clearing any inhaled irritants and microbes in an effort the reduce inflammation. Added to this is the efferocytic activity caused by alveolar macrophages involved in the clearing of cells and tissue in the wake of any injury and infection.
There is an inflammatory persistence and inability to efficiently and effectively get rid of damaged tissues and exhausted immune cells, namely neutrophils, which may be caused by excessive stress that has a negative effect on the phagocytic capacity of alveolar macrophages.
Now, it would be worth mentioning that the presence of airway macrophages can also show a unique phenotype that is complementary with the inclusion of M2 related genes. This gene is most likely to perform its function by responding to any damage to tissues. So, the maintenance of such subpopulation may indeed have a positive effect on the deleterious remodelling within COPD.
There is a critical role to be played by alveolar macrophages when it comes to orchestrating inflammatory to chronic obstructive pulmonary disease (COPD). There is a great increase in the amount of alveolar macrophages present in the lungs of patients suffering with COPD.
This increase in alveolar macrophage numbers is as a result of the increase in recruitment, proliferation and survival. Inflammatory mediators along with oxidants, proteins and proteinases are all secreted by alveolar macrophages as part of a response to coming into contact with smoke extract along with other stimuli.
These products mentioned above are amplified in patients with chronic obstructive pulmonary disease that sees and increase in the secretion of these products that are in direct relation to defective histone deacetylase-2. This can also play a part in the resistance of steroid in the cells of COPD patients.
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