The Emerging Roles of Surfactant Protein-A in Asthma

Abstract

Asthma remains one of the most common respiratory diseases in both children and adults affecting up to 10% of the US population. Asthma is characterized by persistent symptoms, airway inflammation, airflow limitation and frequent exacerbations. Eosinophils are a key immune cell present in a large majority of asthmatics and their presence and dysregulation are clinically associated with more severe asthma. Surfactant protein A (SP-A) provides a first-line of defense in pulmonary innate immunity by virtue of its role in pathogen opsonization. SP-A is known to specifically bind to Mycoplasma pneumoniae (Mp), a pathogen associated with asthma exacerbations, and functions to attenuate Mp pathogenicity and abrogate lung inflammation. In addition, SP-A has been shown to inhibit Mp-induced eosinophil peroxidase (EPO) release, a toxic product that can compromise the integrity of the delicate airway epithelia. We have determined that genetic variation in SP-A2 at position 223 that results in a glutamine (Q) to a lysine (K) substitution alters the ability of SP-A to inhibit EPO release and may offer a mechanistic explanation as to why some SP-A extracted from subjects with asthma is unable to carry out normal immune regulatory functions.

Single Nucleotide Polymorphisms Interactions of the Surfactant Protein Genes Associated With Respiratory Distress Syndrome Susceptibility in Preterm Infants

“…Thus, the absence of SP-A in the exogenous surfactant preparations and the additional surfactant lipids provided by the exogenous preparation may negatively contribute to a further imbalance of pro and anti-inflammatory processes ( 95 ) in the premature lungs. With ongoing trials of SP-A peptides to treat asthma and the use of SP-A peptides to treat RSV ( 97 – 99 ) the present findings point to a future need to investigate SP-A as adjunct therapeutic modality for RDS as well.…”

Preformulation and Evaluation of Tofacitinib as a Therapeutic Treatment for Asthma

“…Eosinophil activation has been implicated in many of the aforementioned symptoms of asthma (17). Further, the severity of the disease may be characterized by the degree of eosinophilia witnessed with some asthmatics, with eosinophilia being defined as the collection of eosinophils in the airway and increased concentration of eosinophils in peripheral blood (18). Therefore, inhibition of JAK proteins may affect the production of these various proinflammatory, immune processes (19,20), resulting in the suppression of eosinophilia (21–23), potentially becoming a novel treatment for eosinophilic asthma.…”

Genetic variation in surfactant protein-A2 alters responses to ozone

“…SP-A is a key immune modulator in the lungs and has much relevance for its role in protecting from various lung diseases. While many publications highlight a role for SP-A in host defense against pathogens (reviewed in [ 16 ]), SP-A has been described as an important mediator in a variety of diseases including cystic fibrosis [ 17 , 18 ], allergic rhinitis [ 19 ], sinusitis [ 20 ], lung cancer metastasis [ 21 ], pulmonary fibrosis [ 22 ], and more recently asthma ([ 3 , 23 , 24 ]) and COPD [ 25 , 26 ]. Given the immense importance of SP-A in the lung, whether by participating directly or mediating indirectly, one can appreciate the need to have an adequate pool of functional SP-A for normal lung homeostasis.…”

“…SP-A and SP-D are known for their immune and host defense properties, aiding in the protection from invading contaminants and limiting an overzealous immune response. SP-A is the most abundant protein in pulmonary surfactant and is generally thought to play a more immune regulatory role than the other surfactant proteins [ 3 ].…”