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
