Exhaled particles as markers of small airway inflammation in subjects with asthma.

Exhaled breath contains suspended particles of respiratory tract lining fluid from the small airways. The particles are formed when closed airways open during inhalation. We have developed a method called Particles in Exhaled air (PExA® ) to measure and sample these particles in the exhaled aerosol. Here, we use the PExA® method to study the effects of birch pollen exposure on the small airways of individuals with asthma and birch pollen allergy. We hypothesized that birch pollen-induced inflammation could change the concentrations of surfactant protein A and albumin in the respiratory tract lining fluid of the small airways and influence the amount of exhaled particles. The amount of exhaled particles was reduced after birch pollen exposure in subjects with asthma and birch pollen allergy, but no significant effect on the concentrations of surfactant protein A and albumin in exhaled particles was found. The reduction in the number of exhaled particles may be due to inflammation in the small airways, which would reduce their diameter and potentially reduce the number of small airways that open and close during inhalation and exhalation.

[Repair effect of Qinbai Qingfei concentrated pellets to AEC-â ¡ of rats infected by Mycoplasmal pneumonia].

To discuss the repair mechanism of Qinbai Qingfei concentrated pellets to AEC-Ⅱ of rats infected by mycoplasma through the observation of the changes and distribution of TGF-ß and SP-A in lungs, totally 60 Wistar rats that weighing 80-100 g were collected, with male and female in half. The rats were divided into six groups randomly, with 10 rats each group, namely blank group, model group, positive group and Qinbai Qingfei concentrated pellets high, middle and low dose groups. Rats were infected through nasal intubation drip of MP. After 10 days of administration, serum and bronchoalveolar lavage fluid (BALF) were collected to detect the concentration of surface activity related protein A (SP-A) by ELISA, left pulmonary tissues of rats were collected to observe the expression and distribution of transforming growth factor-beta (TGF-ß) and SP-A by immunohistochemistry, and right pulmonary tissues were taken to detect TGF-ß and SP-A mRNA expression level by real-time quantitative PCR (RT-PCR). Qinbai Qingfei concentrated pellets can reduce the expression of TGF-ß and increase the expression of SP-A in the lung tissues of rats infected by mycoplasma. Specifically, TGF-ß was mainly distributed among the lung interstitium, while SPAs were mainly distributed in AEC-II and parts of alveolar macrophage. The level of SP-A was reduced in serum and increased in BALF in rats in Qinbai Qingfei concentrated pellets groups. It was proved that Qinbai Qingfei concentrated pellets can restore the normal morphology and function of the lung by reducing the content of TGF-ß to inhibit epithelial-mesenchymal transition (EMT) of alveolar type II epithelial cells and increasing the expression of SP-A. Qinbai Qingfei concentrated pellets have the repairing ability to capillary vessel damage caused by MP in lung tissues of rats.

Immunohistochemical staining of surfactant proteins A and B in skin of psoriatic patients before and after narrow-band UVB phototherapy.

BACKGROUND: Psoriasis is a chronic inflammatory disorder that is mediated by elements of the innate and adaptive immune systems. Surfactant proteins (SPs) play an important role in host defense mechanisms. They are thought to have a potential role in some inflammatory skin diseases including psoriasis. OBJECTIVE: The aim of the study was to evaluate SP-A and SP-B immunohistochemical staining in skin of psoriatic patients before and after narrow-band UV radiation type B (NB-UVB) phototherapy. STUDY DESIGN: Immunohistochemical staining for SP-A and SP-B was performed on tissues from 20 psoriatic patients before and after NB-UVB. Results were compared with the degree of improvement assessed by the Psoriasis Area and Severity Index (PASI) and duration of treatment. RESULTS: In unaffected skin, SP-A and SP-B were restricted to the basal layer; however, in psoriatic skin, they appeared in suprabasal layers in 80% and 85% of cases, respectively. Dermal inflammatory cells showed SP-A in 11 cases (55%) and SP-B in only one case (5%). After treatment by NB-UVB, SP-A and SP-B staining showed predilection to the basal layer. Absence of SP-A staining in suprabasal layers after NB-UVB therapy was correlated to better response to therapy (p=0.003) and shorter duration of treatment (p<0.0001). CONCLUSIONS: SP-A and SP-B positivity is increased in psoriatic skin and reduced after NB-UVB therapy. Absence of SP-A in suprabasal layers after NB-UVB therapy is associated with better response and shorter duration of treatment.

Surfactant protein B inhibits secretory phospholipase A2 hydrolysis of surfactant phospholipids.

Hydrolysis of surfactant phospholipids (PL) by secretory phospholipases A(2) (sPLA(2)) contributes to surfactant damage in inflammatory airway diseases such as acute lung injury/acute respiratory distress syndrome. We and others have reported that each sPLA(2) exhibits specificity in hydrolyzing different PLs in pulmonary surfactant and that the presence of hydrophilic surfactant protein A (SP-A) alters sPLA(2)-mediated hydrolysis. This report tests the hypothesis that hydrophobic SP-B also inhibits sPLA(2)-mediated surfactant hydrolysis. Three surfactant preparations were used containing varied amounts of SP-B and radiolabeled tracers of phosphatidylcholine (PC) or phosphatidylglycerol (PG): 1) washed ovine surfactant (OS) (pre- and postorganic extraction) compared with Survanta (protein poor), 2) Survanta supplemented with purified bovine SP-B (1-5%, wt/wt), and 3) a mixture of dipalmitoylphosphatidylcholine (DPPC), 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC), and 1-palmitoyl-2-oleoyl-phosphatidylglycerol (POPG) (DPPC:POPC:POPG, 40:40:20) prepared as vesicles and monomolecular films in the presence or absence of SP-B. Hydrolysis of PG and PC by Group IB sPLA(2) (PLA2G1A) was significantly lower in the extracted OS, which contains SP-B, compared with Survanta (P = 0.005), which is SP-B poor. Hydrolysis of PG and PC in nonextracted OS, which contains all SPs, was lower than both Survanta and extracted OS. When Survanta was supplemented with 1% SP-B, PG and PC hydrolysis by PLA2G1B was significantly lower (P < 0.001) than in Survanta alone. When supplemented into pure lipid vesicles and monomolecular films composed of PG and PC mixtures, SP-B also inhibited hydrolysis by both PLA2G1B and Group IIA sPLA2 (PLA2G2A). In films, PLA2G1B hydrolyzed surfactant PL monolayers at surface pressures ≤30 mN/m (P < 0.01), and SP-B lowered the surface pressure range at which hydrolysis can occur. These results suggest the hydrophobic SP, SP-B, protects alveolar surfactant PL from hydrolysis mediated by multiple sPLA(2) in both vesicles (alveolar subphase) and monomolecular films (air-liquid interface).

Surfactant protein D decreases pollen-induced IgE-dependent mast cell degranulation.

Mast cells play a key role in allergy and asthma. They reside at the host-environment interface and are among the first cells to make contact with inhaled microorganisms and particulate antigens. Pulmonary surfactant proteins A and D (SP-A and SP-D) function in lung host defense by enhancing microbe phagocytosis and mediating other immune cell functions, but little is known about their effects on mast cells. We hypothesized that SP-A and/or SP-D modulate IgE-dependent mast cell functions. Pollen starch granules (PSG) extracted from Dactylis glomerata and coated with trinitrophenol (TNP) were used as a model of an inhaled organic particulate allergen. Our data revealed that SP-D inhibited by 50% the release of beta-hexosaminidase by peritoneal mast cells sensitized with IgE anti-TNP and stimulated with TNP-PSG. In contrast, SP-A had no effect. Furthermore, SP-D aggregated PSG in a dose-dependent manner, and this aggregation was mediated by SP-D's carbohydrate recognition domain. A single arm SP-D mutant (RrSP-Dser15,20) neither aggregated PSG nor inhibited degranulation, suggesting that multimerization of SP-D is required for maximal PSG aggregation and inhibition of PSG-induced mast cell degranulation. This study is the first to demonstrate that SP-D modulates IgE-mediated mast cell functions, which are important in asthma and allergic inflammation.

Regularity of distribution of immunoreactive pulmonary surfactant protein A in rat tissues.

Existing data has shown that SP-A-like protein or mRNA is widely distributed in lamellar bodies such as tissues and mucosal surfaces. Using immunohistochemistry method with a polyclonal antibody against human SP-A, in this study we investigated distribution of immunoreactive pulmonary surfactant protein A (IR-SP-A) in a number of rat tissues. The SP-A-like immunoreactivity was found in alveolar, parenchyma, pleura of lung; myelin sheath of brain; epithelia of Bowman's capsule, glomerulus and renal tubules of kidney; epithelia of colon, stomach, duct of salivary gland, pharynx; and blood vessel wall and connective tissue of extracellular matrix. The positive signal was blocked by pre-absorbed SP-A antigen from recombinant or bronchoalveolar lavage (BAL). SP-A has long been considered as an important frontier host defense molecule which participates in immune and inflammatory regulation of lung. With every inhalation, small particles, viruses, bacteria, and antigens from environment are continuously deposited onto the vast pulmonary epithelial surface. While a proper host defense is required to protect the lung, an over-exuberant response can disrupt the appropriate balance between pro- and anti-inflammatory. Traditional Chinese medicine believes that body is an open system relevant to the external environment. The physical, chemical and biological environmental factors constantly affect the open system, and the body properly reacts to maintain homeostasis of body machinery. The Chinese traditional medicine scholars have thus hypothesized that 'Qi' (meaning air) is the communication way between the body and external environment. What is 'Qi'? The results from our study suggest that IR-SP-A is a candidate of 'Qi'. It is compatible with the sites, theoretically containing collagenous and lectin domain molecules, also compatible with the primary injury sites of some autoimmune diseases. SP-A may be as one of 'Qi' molecules mentioned in traditional Chinese medicine that trigger some of autoimmune diseases.