Surfactant Protein-A Function: Knowledge Gained From SP-A Knockout Mice

Abstract

Pulmonary surfactant proteins have many roles in surfactant- related functions and innate immunity. One of these proteins is the surfactant protein A (SP-A) that plays a role in both surfactant-related processes and host defense and is the focus in this review. SP-A interacts with the sentinel host defense cell in the alveolus, the alveolar macrophage (AM), to modulate its function and expression profile under various conditions, as well as other alveolar epithelial cells such as the Type II cell. Via these interactions, SP-A has an impact on the alveolar microenvironment. SP-A is also important for surfactant structure and function. Much of what is understood of the function of SP-A and its various roles in lung health has been learned from SP-A knockout (KO) mouse experiments, as reviewed here. A vast majority of this work has been done with infection models that are bacterial, viral, and fungal in nature. Other models have also been used, including those of bleomycin-induced lung injury and ozone-induced oxidative stress either alone or in combination with an infectious agent, bone marrow transplantation, and other. In addition, models investigating the effects of SP-A on surfactant components or surfactant structure have contributed important information. SP-A also appears to play a role in pathways involved in sex differences in response to infection and/or oxidative stress, as well as at baseline conditions. To date, this is the first review to provide a comprehensive report of the functions of SP-A as learned through KO mice.

The alveolar macrophage toponome of female SP-A knockout mice differs from that of males before and after SP-A1 rescue

“…It has also been identified in a variety of other tissues, including the intestine 1 , the nasal epithelium 2 , and the female genital tract 3 , as well as other sites. SP-A has been classified as a collectin or calcium-dependent collagenous lectin based on the fact that it contains a collagenous domain and a Ca +2 -dependent carbohydrate recognition domain that binds specific carbohydrate components of cells, microorganisms, and carbohydrate-containing macromolecules in the lung 4 .…”

“…SP-A, like other collectins (including, but not limited to the mannose-binding lectin, complement C1q, conglutinin, and SP-D) appears to be of particular importance in host defense 4 – 7 . SP-A binds various pathogens, allergens, and particulates, affecting their recognition by immune cells.…”

“…This action is mediated by NF-κB 13 following the interaction of SP-A with TLR2 16 . SP-A also has significant stimulatory effects on bacterial phagocytosis 4 , 5 , both directly by serving as an opsonin 17 , 18 , and indirectly by enhancing the activity of the AM 19 – 21 . SP-A also causes changes in the AM proteome 22 – 24 , the actin cytoskeleton 25 , the miRNome 26 – 28 , and the toponome, the spatial network of potentially interacting proteins within the cell 29 , 30 .…”

“…SP-A also causes changes in the AM proteome 22 – 24 , the actin cytoskeleton 25 , the miRNome 26 – 28 , and the toponome, the spatial network of potentially interacting proteins within the cell 29 , 30 . All of these actions are likely to influence host defense function 4 . An important example of the benefit of SP-A is shown by the greatly reduced survival in experimental bacterial or viral pneumonia models of mice lacking SP-A (SP-A knockout; KO) versus wild type mice 31 – 34 .…”

“…A number of studies have shown that the response to SP-A is sexually dimorphic 4 , 10 , 25 – 28 , 35 , 38 and that sex hormones play a role 39 . Several studies investigating sex differences in survival and various AM processes under different conditions have concluded that females are more immunocompetent than males 24 , 26 , 28 , 35 , 38 , 40 – 42 .…”