White blood cells called neutrophils aid in the recovery of injured tissues and the eradication of infections. Since they are the most prevalent form of white blood cell in the body, they serve as the first line of defense in the healing and infection-fighting processes. Infections, wounds, pharmacological treatments, some hereditary disorders, and stress can cause a rise or decrease in neutrophil counts. These neutrophils have a significant impact on a variety of pathological states and disorders. A group of researchers, including Amarjit Mishra, Assistant Professor at Auburn University, Yujie Guo, Li Zhang, Sunil More, Tingting Weng, and others, have recently conducted additional research on the function of neutrophils and their recruitment at a site. They have discovered that these neutrophils participate in a crucial process connected to acute lung injury.
Acute lung injury is a progressive syndrome that develops directly from pneumonia, gastric acid aspiration or inhalation of toxic gases, or indirectly from extrapulmonary sepsis or trauma. It is characterized by acute inflammation with neutrophil infiltration, alveolar-capillary barrier damage, pulmonary edema and arterial hypoxemia. Acute lung injury is a disorder of acute inflammation that causes disruption of the lung endothelial and epithelial barriers. Acute lung injury remains a significant source of morbidity and mortality in the critically ill patient population. Acute lung injury has a high incidence (200,000 per year in the US) and overall mortality remains high.
Understanding of the pathology of acute lung injury by Amarjit Mishra
Acute lung injury is a progressive syndrome that can result either directly from extrapulmonary infection or trauma, pneumonia, stomach acid aspiration, or inhalation of poisonous gases. Acute inflammation with neutrophil infiltration, pulmonary edoema, arterial hypoxemia, and disruption to the alveolar-capillary barrier are its defining features. A disease of acute inflammation known as acute lung injury results in the disruption of the endothelium and epithelial barriers in the lung. A prominent cause of morbidity and mortality in the critically sick patient population is still acute lung damage. The incidence of acute lung injury is considerable (200,000 per year in the US), and overall mortality is still high. However, because of inconsistent definitions, etiologic variances, regional variations, limited recording, and underrecognition of disease entities, the occurrences of acute lung injury have been challenging to estimate. In light of this, it is crucial to understand the pathology of acute lung injury. Scientists like Amarjit Mishra, who have carried out substantial laboratory-based research to understand the mechanism, have recognised the need to perform such a study.
The neutrophils connected to the respiratory system are called pulmonary neutrophils. They are essential for innate immunity because they are the first inflammatory cells to be enlisted upon lung damage. The pathogenesis of acute lung damage is largely dependent on neutrophil migration into the lungs. By phagocytizing microorganisms, these neutrophils play a significant part in innate immunity. The extracellular release of antimicrobial agents like reactive oxygen species, proteases, and cationic peptides occurs when neutrophils are recruited excessively and activated for an extended period of time, which frequently results in lung injury, including damage to endothelial and epithelial cells. But the researchers discovered that abnormal neutrophil recruitment causes lung damage. By conducting a number of experiments on mice and murine models of acute lung injury, it was discovered.
Amarjit Mishra’s significant research was centered on the type I transmembrane protein known as VCAM-1, which belongs to the immunoglobulin superfamily. The membrane-bound version of VCAM-1, which is present on the surface of leukocytes, binds to the integrins α4β1 and α4β7. It has been linked to asthma because it regulates the rolling and adhesion of monocytes, lymphocytes, and eosinophils via the α4β1 integrin in the vasculature. Via proteolytic cleavage, VCAM-1 can also be released as the soluble form, sVCAM-1. Using a variety of experiments, it was discovered that cytochalasin treatment had no discernible effects on the migration of bone marrow neutrophils while sVCAM-1 boosted the migration of untreated neutrophils.
Researchers led by Amarjit Mishra of Auburn University have demonstrated in this study for the first time that acute lung injury results in the release of VCAM-1 from AEC I. In alveoli, it is a significant source of sVCAM-1. AEC I, but not AEC II or alveolar macrophages, had significantly higher levels of VCAM-1 expression. The inflammatory cytokine IL-β1 stimulates the release of sVCAM-1 during acute lung damage, which further boosts neutrophil infiltration.
The idea that sVCAM-1 is produced from AEC I by ADAM-17-induced activation of P2X7R via the ERK pathway is supported by a number of lines of evidence. In conclusion, Amarjit Mishra described a novel method by which P2X7R on AEC I controls the release of VCAM-1, which attracts pathogenic neutrophils via β1 integrins and serves as a neutrophil chemoattractant and a macrophage activator.
Targeting sVCAM-1 has been shown to be a possible therapeutic option, according to this unconventional finding by Amarjit Mishra of Auburn University and his colleagues. It may assist in preventing pathogenic neutrophil recruitment or infiltration. As it does not obstruct the physiological recruitment of neutrophils needed for regular defense mechanisms, this can also be a potential therapy target.