The role of giant multinucleated cells in asthma in horses deserves more attention, according to researchers.
Giant multinucleated cells (GMCs) are a result of the fusion of monocytes and macrophages. They are considered a marker of chronic inflammation.
Macrophages are normal resident cells within the lungs of horses. However, the clinical implication of the presence of activated or fused macrophages – GMCs – has largely been overlooked.
In tissues, the presence of GMCs is assumed to represent a specialization for improved phagocytosis – the cellular process for ingesting and eliminating the likes of microorganisms, foreign substances, and dying cells.
Molecular pathways leading to GMC formation are many and represent an emerging research field, Ilaria Basano and her fellow researchers noted in the journal Animals.
It is recognized that interleukin-4, a cytokine whose role has been highlighted in severe equine asthma, is likely to play a major role in this process.
The researchers, in a study at the University of Turin in Italy, looked at the prevalence of GMCs in bronchoalveolar lavage fluid – that’s fluid collected for analysis after being washed through the lungs.
They hypothesised that GMCs would be more common in horses with equine asthma compared to controls, and that their numbers would be higher in severe cases.
Equine asthma is currently diagnosed by the presence of increased numbers of neutrophils, mast cells and/or eosinophils in lavage fluid.
In their study, they analysed lavage washes from 34 asthmatic horses and compared the results to those from lavage fluid from 10 control horses.
GMCs were frequently seen in both asthmatic and control horses, with an increased prevalence in those with equine asthma. They were seen in almost all the asthmatic horses, and 70% of the control horses.
The ratio of GMCs to macrophages was significantly higher in severe cases of asthma than in mild to moderate cases and control horses.
In asthmatic horses, an increase in this ratio was significantly associated with lavage mastocytosis – an abnormal buildup of mast cells.
Abnormally rapid breathing was the only clinical sign that tended to be positively associated with a higher ratio of GMCs to macrophages.
The research team said their findings suggest a relationship might exist between molecular mechanisms regulating GMC formation and mast cell recruitment in the equine lung.
The same mechanisms could lead to rapid breathing, even in the absence of respiratory effort at rest.
The high number of control horses with evidence of GMCs could well be related to the horses being naturally exposed to dust of biological, vegetal, or mineral origin, they said.
“It is reasonable to hypothesize that a dust-rich environment stimulates GMC formation in the lungs, even in the absence of pulmonary diseases.”
They suggested including a GMC count in the basic analysis of lung lavage samples to gain more insights into their role in equine asthma. Their possible role in equine asthma deserves further research attention, they concluded.
Their increased prevalence in severe asthma and their significant association with mast cells and, to a lesser extent, relative neutrophil cell counts in lavage fluid, suggest a regulatory role in disease. This is in line with recent evidence showing alveolar macrophages, the precursors of GMCs, as important orchestrators in equine asthma development.
The study team comprised Basano, Alessandra Romolo, Giulia Iamone, Giulia Memoli, Barbara Riccio, Barbara Miniscalco and Michela Bullone, all with the University of Turin; and Jean-Pierre Lavoie, with the University of Montreal in Canada.
Basano, I.; Romolo, A.; Iamone, G.; Memoli, G.; Riccio, B.; Lavoie, J.-P.; Miniscalco, B.; Bullone, M. Giant Multinucleated Cells Are Associated with Mastocytic Inflammatory Signature Equine Asthma. Animals 2022, 12, 1070. doi.org/10.3390/ani12091070