Alveolar macrophages (AMs) are lung-resident myeloid cells that sit at the interface of the airway and lung tissue. Under homeostatic conditions, their primary function is to clear debris, dead cells and excess surfactant from the airways. They also serve as innate pulmonary sentinels for respiratory pathogens and environmental airborne particles and as regulators of pulmonary inflammation. However, they have not typically been viewed as primary therapeutic targets for respiratory diseases. Here, we discuss the role of AMs in various lung diseases, explore the potential therapeutic strategies to target these innate cells and weigh the potential risks and challenges of such therapies. Additionally, in the context of the COVID-19 pandemic, we examine the role AMs play in severe disease and the therapeutic strategies that have been harnessed to modulate their function and protect against severe lung damage. There are many novel approaches in development to target AMs, such as inhaled antibiotics, liposomal and microparticle delivery systems, and host-directed therapies, which have the potential to provide critical treatment to patients suffering from severe respiratory diseases, yet there is still much work to be done to fully understand the possible benefits and risks of such approaches.

Bisphenol A (BPA), a monomer of polycarbonate plastics and epoxide resin, is a high-production-volume chemical implicated in asthma pathogenesis when exposure occurs to the developing fetus. However, few studies have directly examined the effect of in utero and early-life BPA exposure on the pathogenesis of asthma in adulthood. This study examines the influence of perinatal BPA exposure through maternal diet on allergen sensitization and pulmonary inflammation in adult offspring. Two weeks before mating, BALB/c dams were randomly assigned to a control diet or diets containing 50 ng, 50 μg or 50 mg BPA/kg of rodent chow. Dams remained on the assigned diet throughout gestation and lactation until postnatal day (PND) 21 when offspring were weaned onto the control diet. Twelve-week-old offspring were sensitized to ovalbumin (OVA) and subsequently challenged with aerosolized OVA. Sera, splenocytes, bronchoalveolar lavage fluid and whole lungs were harvested to assess allergen sensitization and pulmonary inflammation after OVA challenge. Serum anti-OVA IgE levels were increased two-fold in offspring exposed to 50 μg and 50 mg BPA/kg diet, compared with control animals. In addition, production of interleukin-13 and interferon-γ were increased in OVA-stimulated splenocytes recovered from BPA-exposed mice. Pulmonary inflammation, as indicated by total and differential leukocyte counts, cytokines, chemokines and pulmonary histopathology inflammatory scores, however, was either not different or was reduced in offspring exposed to BPA. Although these data suggest that perinatal BPA exposure beginning before gestation enhances allergen sensitization by increasing serum IgE and splenocyte cytokine production, a substantial impact of BPA on OVA-induced pulmonary inflammation in adulthood was not observed.