Editorial: Odyssey of Surfactant Proteins SP-A and SP-D: Innate Immune Surveillance Molecules

Surfactant protein A (SP-A) and D (SP-D) are hydrophilic collagenous C-type lectins, which were originally discovered in the lungs associated with surfactant phospholipids. It was later shown that the two proteins, unlike hydrophobic surfactant proteins, SP-B and SP-C, are keenly involved in protecting lungs against insults from pathogens, allergens, apoptotic, and necrotic cells (1). Two aspects became clear in subsequent years that (i). SP-A and SP-D have extra-pulmonary existence; and (ii). They can manipulate immune cells, and thus, regulate inflammatory responses (2). Although there have been a constant debate about their candidate receptor(s)—there are several reported so far (1). Much of the immunological studies, beyond interaction with surfactant system and pathogens, have been followed up toward SP-D. It has become apparent that SP-D is an innate immune surveillance molecule at the mucosal surfaces, which can act as a bridge between innate and adaptive immunity. The role of SP-D in modulating antigen presentation, helper T cell polarization and B cell differentiation and class switching (3) are few neat examples. This volume comprises 14 papers that extend our knowledge on SP-A and SP-D, and their roles in infection, inflammation and cancer. A consistent theme discussed by several contributors is the differential role of two forms of SP-A in oxidative stress and lung innate immunity (Thorenoor, Umstead et al.; Nalian et al.; Thorenoor, Kawasawa et al.; Wang et al.). In humans, there are two SP-A variants differing in the collagen region, SP-A1 and SP-A2, encoded by SFTPA1 and SFTPA2, respectively, and produced by the alveolar type II cells in the lung. Importantly, SP-A1 and SP-A2 seem to differentially bind to phagocytic, but not to non-phagocytic cells (Thorenoor, Umstead et al.). SP-A1 and SP-A2 differentially bind and regulate neonatal and adult human alveolar macrophages (AMs) (Thorenoor, Umstead et al.). AMs from transgenic mice expressing human SP-A1 and SP-A2 exhibit differential expression of cell surface proteins (Thorenoor, Kawasawa et al.) Rodents express only one SP-A variant; thus, Nalian et al. have compared the rodent and human SP-A with respect to structural determinants of the function. The data infers that mouse SP-A is a functional hybrid of human SP-A1 and SP-A2. Particularly striking in this regard is the differential response in the two sexes. Humanized transgenic (hTG) male and female mice, carrying both SP-A1/SP-A2 (6A2/1A0, co-expressed) and SP-A-gene deficient mice were exposed to filtered air (FA) or ozone (O3), and miRNA levels were measured in isolated AMs (Thorenoor, Kawasawa et al.). The AM miRNome of co-expressed females was significantly downregulated in response to ozone induced oxidative stress. Several of the validated miRNA targets were involved in pro-inflammatory response, anti-apoptosis, cell cycle, cellular growth, and proliferation (Thorenoor, Kawasawa et al.). Continuing with this