Novel role of surfactant protein A in bacterial sinusitis

Abstract

Background Chronic rhinosinusitis (CRS) is a common inflammatory disorder of the upper airway characterized by chronic inflammation and significant sinonasal remodeling. CRS has two major subgroups based on whether polyps are present or absent. In some cases, it is characterized by colonization with opportunistic pathogens such as Pseudomonas aeruginosa (PA), Staphylococcus aureus and other bacteria. The innate immune system of the sinonasal epithelium is the first line of defense against inhaled pathogens. Surfactant protein A (SP-A) is a member of the collectin family secreted by the airway epithelia that plays a critical role in airway innate immunity, as it can aggregate bacteria. We hypothesized that SP-A plays a role in bacterial CRS. Methods Air-liquid-interface (ALI) cultures of nasal epithelial cells were derived from human ex vivo healthy and CRS sinus tissues (n=26) and challenged with PA. SP-A levels were measured with Western Blot and qRT-PCR in ALI and sinus tissues. Results We determined that SP-A i) mRNA and protein levels are significantly increased in CRS tissues compared to healthy sinuses; ii) although primary expressed in the lung, it is also synthesized and expressed in sinonasal epithelia; ii) is expressed in the sinuses of an SP-A humanized transgenic mouse but not in SP-A knock-out mouse; iv) mRNA levels are upregulated significantly during PA challenge, but protein levels are downregulated 4h post challenge and upregulated at 12h. Conclusions Our data suggest that SP-A is expressed in the sinuses and it plays a role in the sinus innate immune responses during bacterial infections.

Future topical medications in chronic rhinosinusitis

“…Surfactant is a major component of the innate immune system; it mainly consists of phospholipids that biologically coat the gel layer, reducing the surface tension and the mucous viscosity in the respiratory system . Recent studies have suggested that surfactant protein A is expressed in the sinuses and that it plays a role in the sinus innate immune responses during bacterial infections . Furthermore, the antimicrobial potential secondary to the ability to disrupt cell membranes and eradicate bacterial biofilms is also described as a therapeutic benefit of surfactants in the setting of CRS .…”

The innate immune system and beyond

“…The innate immune system is a common theme in several of the articles in this month's issue of the International Forum of Allergy & Rhinology ( IFAR ). The innate immune system is made up of the transmembrane proteins toll‐like receptors (TLRs) that are able to recognize consistencies found in various pathogens . These patterns are referred to as pathogen‐associated molecular patterns (PAMPs) and include highly conserved structures that are unique to the bacterial organisms.…”

“…These patterns are referred to as pathogen‐associated molecular patterns (PAMPs) and include highly conserved structures that are unique to the bacterial organisms. Structures such as the frequency of a cytosine nucleotide followed by a guanine nucleotide, lipopolysaccharides in gram‐negative bacteria, and lipoteichoic acid in gram‐positive bacteria can all stimulate a TLR, activating the innate immune system . Once activated, antimicrobial cytokines, chemokines, proteins, and peptides are released.…”

“…Lymphocytes and phagocytes are also activated to target the pathogen. As Noutsios et al . from the University of Arizona nicely state, the innate immune system is the body's first line of defense against inhaled pathogens and when compromised, said pathogens can lead to acute and chronic states of inflammation and infection.…”

“…It can recognize various PAMPs, bind to cell walls, inhibit bacterial growth, and facilitate opsonization. In their study, they demonstrate the expression of SP‐A in cultured sinonasal epithelium cells as well as a humanized transgenic mouse, upregulation in chronic rhinosinusitis (CRS) tissues compared to healthy tissues, and significant upregulation in cell culture when exposed to Pseudomonas aeruginosa …”