Role of resistin like molecule a in pulmonary arterial remodeling induced by the response to antigen and urban particulate matter

Abstract Our studies focused on the role of resistin like molecule α (RELMα) in severe pulmonary arterial remodeling induced by a T helper 2 (Th2) response to antigen. We studied wild type and RELMα deficient mice following immunization with Ovalbumin (OVA) complexed to Alum and exposure to soluble OVA alone or in combination with respirable urban particulate matter. The urban particulate matter (PM2.5) was collected from the air in New York City. Our studies demonstrated a significant exacerbation of pulmonary arterial remodeling in antigen primed wild type mice exposed to a combination of antigen and urban particulate matter. RELMα deficient mice, in contrast, failed to show the exacerbation and developed pulmonary arterial thickening to exposure with antigen and respirable urban particulate matter to a significantly smaller degree relative to wild type. The severity of inflammation and the type of the immune response in the RELMα deficient mice challenged with antigen or the combination of antigen and urban particulate matter was not significantly different from the responses in wild type mice. RELMα is known to have a critical role in hypoxia induced pulmonary arterial remodeling and to be induced by hypoxia. Airborne metals mimic hypoxia induced cell signaling. Therefore, our data suggest the idea that both antigen and urban pollution induce RELMα signaling via two independent, but additive pathways.