Protective role of the lung collectins surfactant protein A and surfactant protein D in airway inflammation

Abstract

The acute inflammatory airway response is characterized by a time-dependent onset followed by active resolution. Emerging evidence suggests that epithelial cells of the proximal and distal air spaces release host defense mediators that can facilitate both the initiation and the resolution part of inflammatory airway changes. These molecules, also known as the hydrophilic surfactant proteins (surfactant protein [SP]–A and SP-D) belong to the class of collagenous lectins (collectins). The collectins are a small family of soluble pattern recognition receptors containing collagenous regions and C-type lectin domains. SP-A and SP-D are most abundant in the lung. Because of their structural uniqueness, specific localization, and functional versatility, lung collectins are important players of the pulmonary immune responses. Recent studies in our laboratory and others indicated significant associations of lung collectin levels with acute and chronic airway inflammation in both animal models and patients, suggesting the usefulness of these molecules as disease biomarkers. Research on wild-type and mutant recombinant molecules in vivo and in vitro showed that SP-A and SP-D bind carbohydrates, lipids, and nucleic acids with a broad-spectrum specificity and initiate phagocytosis of inhaled pathogens as well as apoptotic cells. Investigations on gene-deficient and conditional overexpresser mice indicated that lung collectins also directly modulate innate immune cell function and T-cell–dependent inflammatory events. Thus, these molecules have a unique, dual-function capacity to induce pathogen elimination and control proinflammatory mechanisms, suggesting a potential suitability for therapeutic prevention and treatment of chronic airway inflammation. This article reviews evidence supporting that the lung collectins play an immune-protective role and are essential for maintenance of the immunologic homeostasis in the lung.

The role of mannose-binding lectin in pneumococcal infection

“…By contrast, our results suggest that MBL deficiency may be associated with higher severity of P-CAP. However, studies aimed to analyse the role of genetic variability of the MBL gene in infectious diseases, particularly respiratory, should be aware of the existing LD among MBL2 and the genes of SP-A1, -A2 and -D. Identification of new pathways and molecules involved in susceptibility to and severity of respiratory infectious diseases could lead to new therapeutic approaches, and the therapeutic use of MBL and SPs has been advocated [15,16,33]. Large studies designed to analyse the genetic variability in the region of chromosome 10 containing these genes are desirable in order to unravel their role in susceptibility and severity of pneumococcal infection, particularly P-CAP.…”

“…regulation of the inflammatory response, as well as in clearance of apoptotic cells [15,16]. SPs, but not MBL, take part in the first-line host defence in healthy lung.…”

“…Genetic variability at genes coding for these SPs was associated with higher susceptibility and poor outcome of CAP [17]. The human SP-A locus consists of two similar genes, SFTPA1 and SFTPA2, localised within a cluster (10q21-24) that includes the SP-D gene (SFTPD) [15]. MBL2 was reported not to be in physical linkage with the genes of these SPs [18], but no studies of linkage disequilibrium (LD) of MBL2 with SFTPA1, SFTPA2 or SFTPD have been performed to date.…”

Surfactant Protein D (Sp-D) Binds to Membrane-proximal Domain (D3) of Signal Regulatory Protein α (SIRPα), a Site Distant from Binding Domain of CD47, while Also Binding to Analogous Region on Signal Regulatory Protein β (SIRPβ)

“…direct binding to pathogens, leading to enhanced uptake by scavenger cells and binding to surface receptors involved in immunity, resulting in the modulation of the receptor function (14,45). Indeed, Sp-D has been reported to bind CD14 in a calcium-and carbohydrate-dependent manner (35).…”

C1q Deficiency Promotes Pulmonary Vascular Inflammation and Enhances the Susceptibility of the Lung Endothelium to Injury

“…Like their structurallyrelated plasma counterparts, SP-A and SP-D are highly effective at opsonizing microbes and aiding in the clearance of cellular and non-cellular debris from the lung (10 -12). Additionally, these proteins have been shown to exhibit other important immunological functions such as inhibiting resting alveolar macrophage activation and modulating their pro-inflammatory responses (13)(14)(15).…”