The Different Faces of Macrophage in Asthma

Introduction:

Asthma is a state with inflammation, contracted muscles of airways with the addition of mucus secretion. It is a lung disease that cannot be cured completely. During this state, the patient can go through many changes in the body. Some of the common changes at the histologic levels are eosinophil inflammation, the epithelial layer getting desquamated and enlarged, basement membranes getting thickened, and smooth muscle cells getting enlarged. The macrophages also show inflammatory responses by releasing pro-inflammatory cytokines like interleukin -1beta, TNFalpha, and CD cells. This topic describes the different faces of macrophages in asthma and the therapeutic strategies involved in overcoming the macrophage faces of asthma.

What Is Asthma?

Asthma is a chronic lung disease in which the airways get swelled and narrowed. It is not curable completely; however, it can reverse. Asthma can be minor but it hampers the daily activities of the patient. So, the patient dealing with asthma requires medication to ease the airflow. Constricted muscles, airway inflammation, and mucus production accompany asthma. The symptoms involved in asthma patients are chest tightening with pain, cough, wheezing, and shortness of breath. It can be caused by allergy or can be non-allergic too. On observing the asthmatic changes on microscopic levels, the blood shows changes with an increase in eosinophils and neutrophils with the involvement of macrophages. Asthma can be of different types, like persistent or intermittent depending on how frequent the asthma attack comes or pediatric or adult, depending on the age of the patient, or allergic or non-allergic, depending on the causes of asthma.

What Happens to Macrophages in Asthma?

Macrophages are the type of large white blood cells that kill microorganisms by engulfing them through the process called phagocytosis. They also remove foreign bodies and dead cells from the body, which is called efferocytosis. These cells are found in the lung, liver, brain, bones, and blood.

Macrophages are present excessively in the lungs, and they contribute to the actions of asthma by changing their functions of phagocytosis and efferocytosis instead of increasing their numbers. Alveolar macrophages are also found in the sputum of asthmatic patients.

What Are the Changes in Macrophage Function During Asthma?

Phagocytosis:

• Macrophages have the function of phagocytosis, which eliminates pathogens and other foreign bodies by recognizing and engulfing them. This process of phagocytosis shows an important role in innate immunity.

• Mainly CD macrophages use to perform the activities, but due to the effects of asthma, the activity of macrophages changed.

• The phagocytosis of the airway macrophages got impaired.

• Even the staphylococcus bacteria got less phagocytosed by macrophages, and less neutrophil activity was seen.

• It was also noted that the sulfur colloid particles were more in lung macrophages during asthma.

• The CD163 macrophage activity was found more in the lungs and even in the sputum of asthmatic patients.

Efferocytosis:

• The clearance of the dead cells is called efferocytosis. This process initiates the anti-inflammatory actions by producing Interleukin-10.

• The levels of interleukin-10 got less in asthma, which shows the impairment of efferocytosis.

• The activity of the efferocytosis of the dead bronchial epithelial cells by the macrophages of the lungs (sputum) got impaired.

Inflammation:

• Macrophages also show inflammation reactions in asthmatic patients.

• Asthma can lead to altered cytokine formation and altered phagocytosis.

• Due to inflammation, more M1 and M2 macrophages were seen in the lungs of asthmatic patients.

• But the effects of M1 or M2 depend more on different types of asthma. M1 is related to neutrophils, and M2 is related to eosinophils release.

• As changes in macrophages are found in asthma, different types of asthma can also lead to changes or the release of different types of cytokines.

• Macrophages that are involved in the chronic inflammation of asthma are seen as producing more pro-inflammatory cytokines, such as TNFalpha and interleukin-1beta.

• Inflammasomes are multiprotein that identify the microorganisms and release cytokines. Such inflammasomes like interleukin -1beta and NLRP3 are also present in the development of asthma.

• The levels of NLRP3 in the blood present the severity of asthma.

• Less number of interleukin-10 macrophages leads to the pathogenesis of asthma.

Tissue Remodeling:

• Due to airway remodeling, collagen deposition, excessive mucus secretion, and airway activity got increased.

• CD206 activity also got more in asthmatic patients. It was also reported that M2 macrophages also got increased in asthma.

What Are New Strategies That Target Macrophages in Asthma?

Many therapeutic techniques target macrophages in asthma state. The treatments include macrolides, corticosteroids, statins, and phosphodiesterase inhibitors; all are used to control the effects of asthma.

Targeting Phagocytosis and Efferocytosis: When the treatment targets the phagocytosis and efferocytosis of the alveolar macrophages, it is important for lung functions and stability.

• Angiotensin was used to increase the effects of efferocytosis.

• Galectin-3 was quite a useful product in increasing the effects of efferocytosis by the monocytes-derived macrophages.

• Hydrogen gas inhalation can improve the activity of phagocytosis by the alveolar macrophages.

Modulating Inflammation: Inflammation is also one of the symptoms that contribute to asthma.

• So, to control inflammation in asthmatic patients, the use of corticosteroids is done, which results in anti-inflammatory effects by suppressing the cytokines, interleukin-1beta, and increasing the interleukin -10.

• Another drug Brevenal (anti-inflammatory), which was used to cause less release of CD86 (M1) and CD206 (M2), leads to lesser involvement of cytokines and less inflammation.

• Inflammation can be controlled by the use of the cytokines-releasing inhibitory drug CRID3, which blocks the hyperresponsiveness and inflammation by the macrophages in the lungs.

• Estrogens are one of the products that can control allergy-induced asthma inflammation.

Conclusion:

Asthma is a chronic lung disease accompanied by inflammation and muscle contraction of the airways. These asthma patients have macrophages released during the asthmatic state. Macrophages in asthma go through an altered functioning for phagocytosis and efferocytosis. Macrophages lead to the release of CD and pro-inflammatory cytokines like interleukin -10. The new strategies to stabilize the lung and macrophage functioning are also listed above. Some of the new treatments include the use of corticosteroids, Galectin-3, and hydrogen inhalation by asthmatic patients to lessen asthma actions by overcoming the macrophage's changed reactions and functions.