Effects of ageing and smoking on SP-A and SP-D levels in bronchoalveolar lavage fluid

Betsuyaku, Tomoko; Kuroki, Yoshio; Nagai, Katsura; Nasuhara, Yasuyuki; Nishimura, Masaharu

doi:10.1183/09031936.04.00064004

Cited by 87 publications

(78 citation statements)

References 31 publications

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“…The latter is in agreement with published observations where although decreased SP-A levels as a function of age were found in bronchial lavage, no alterations in SP-A levels were observed in alveolar lavage (7). Of interest, in the present study, we observed that the proportion of SP-A1 declined with age.…”

Section: Discussionsupporting

confidence: 82%

“…Reports for cystic fibrosis (CF) have shown decreased levels of SP-A in children (26,65), increased levels associated with bacterial infection (59), and normal-to-increased levels with airway infection (37). In a recent study, a decrease in SP-A content was observed with increasing age in bronchial lavage, but not in alveolar lavage (7). Moreover, SP-A genetic variant associations with various lung diseases, including RDS (15,66), RSV (52), IPF (71), and tuberculosis (17), have also been reported.…”

mentioning

confidence: 98%

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Characterization of a human surfactant protein A1 (SP-A1) gene-specific antibody; SP-A1 content variation among individuals of varying age and pulmonary health

Tagaram¹,

Wang²,

Umstead³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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The human surfactant protein A (SP-A) locus consists of two functional genes (SP-A1, SP-A2) with gene-specific products exhibiting qualitative and quantitative differences. The aim here was twofold: 1) generate SP-A1 genespecific antibody, and 2) use this to assess gene-specific SP-A content in the bronchoalveolar lavage fluid (BALF). An SP-A1-specific polyclonal antibody (hSP-A1_Ab 68-88 _Col) was raised in chicken, and its specificity was determined by immunoblot and ELISA using mammalian Chinese hamster ovary (CHO) cell-expressed SP-A1 and SP-A2 variants and by immunofluorescence with stably transfected CHO cell lines expressing SP-A1 or SP-A2 variants. SP-A1 content was evaluated according to age and lung status. A gradual decrease (P Ͻ 0.05) in SP-A1/SP-A ratio was observed in healthy subjects (HS) with increased age, although no significant change was observed in total SP-A content among age groups. Total SP-A and SP-A1 content differed significantly between alveolar proteinosis (AP) patients and HS, with no significant difference observed in SP-A1/SP-A ratio between AP and HS. The cystic fibrosis (CF) ratio was significantly higher compared with AP, HS, and noncystic fibrosis (NCF), even though SP-A1 and total SP-A were decreased in CF compared with most of the other groups. The ratio was higher in culture-positive vs. culture-negative samples from CF and NCF (P ϭ 0.031). A trend of an increased ratio was observed in culture-positive CF (0.590 Ϯ 0.10) compared with culture-positive NCF (0.368 Ϯ 0.085). In summary, we developed and characterized an SP-A1 gene-specific antibody and used it to identify gene-specific SP-A content in BALFs as a function of age and lung health. alveolar proteinosis; bronchoalveolar lavage fluid; cystic fibrosis; peptide antibody; surfactant protein A HUMAN SURFACTANT PROTEIN A (SP-A), a member of the C-type lectin or collectin family, is encoded by two functional genes, SP-A1 and SP-A2, with a high percentage of sequence similarity detected at the nucleotide (94%) and the amino acid (aa) (96%) levels. More than 30 alleles have been characterized for these two genes, with four SP-A1 alleles (6A, 6A 2 , 6A 3 , and 6A 4 ) and six SP-A2 alleles (1A, 1A 0 , 1A 1 , 1A 2 , 1A 3 , and 1A 5 ) most frequently observed in the general population (10,14,16,40,67). Although a high level of sequence similarity is shared among the SP-A genes and their corresponding alleles, in vitro studies have identified both qualitative (22,36,57,60,77,80,81) and quantitative (24,35,38,46,56,69,70,78,79) differences between the two genes.Qualitative differences between the SP-A1 and SP-A2 genes include functional, structural, and biochemical differences. Functionally, SP-A2 exhibits a higher level of activity than SP-A1 in its ability to enhance TNF-␣ and IL-8 production by the macrophage-like THP-1 cell line (80, 81), phagocytosis of Pseudomonas aeruginosa by rat alveolar macrophages (57), and secretion of phosphatidylcholine by type II alveolar cells (77). Structurally, circular dichroic spectroscopy stud...

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Section: Discussionsupporting

confidence: 82%

mentioning

confidence: 98%

Characterization of a human surfactant protein A1 (SP-A1) gene-specific antibody; SP-A1 content variation among individuals of varying age and pulmonary health

Tagaram¹,

Wang²,

Umstead³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…PC phosphatidylcholine, POPC 1-palmitoyl,2-oleoyl-sn-glycero-3-phosphocholine, DPPC 1,2-dipalmitoyl-sn-glycero-3-phosphocholine increase in neutrophils in human ALF as a marker of acute and/or chronic inflammation, i.e., from 2 % total neutrophils in ALF from healthy adults (mean age 28) to 8 % in ALF from idiopathic pulmonary fibrosis patients (mean age 58). However, similar studies from the same authors showed that healthy young adults have more neutrophils in their ALF than elderly subjects (1.1 vs. 0.3 %, respectively) (Betsuyaku et al 2004). Although we were unable to acquire the cytological data from our human samples, our mouse cytological data showed a similar trend with a relatively low number of neutrophils in ALF from young and old mice (4.41 and 3.1 %, respectively), indicating that the basal lung inflammation observed in aging may not be driven solely by an influx of neutrophils into the alveolar space in the absence of other stimuli.…”

Section: Discussionmentioning

confidence: 94%

“…Human studies comparing adults vs. middle-aged/elderly subjects that normalized by recovered ALF volume showed a slight decrease in SP-A and no differences in SP-D with age (Betsuyaku et al 2004). However, in this study (Betsuyaku et al 2004), the ALF recovery among subjects varied, and thus, as pointed out by the authors, this may affect the comparisons made between age groups. This problem does not exist in our study since we normalized samples by protein amount.…”

Section: Discussionmentioning

confidence: 99%

Molecular composition of the alveolar lining fluid in the aging lung

Moliva

Rajaram

Sidiki

et al. 2014

AGE

103

121

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As we age, there is an increased risk for the development of pulmonary diseases, including infections, but few studies have considered changes in lung surfactant and components of the innate immune system as contributing factors to the increased susceptibility of the elderly to succumb to infections. We and others have demonstrated that human alveolar lining fluid (ALF) components, such as surfactant protein (SP)-A, SP-D, complement protein C3, and alveolar hydrolases, play a significant innate immune role in controlling microbial infections. However, there is a lack of information regarding the effect of increasing age on the level and function of ALF components in the lung. Here we addressed this gap in knowledge by determining the levels of ALF components in the aging lung that are important in controlling infection. Our findings demonstrate that pro-inflammatory cytokines, surfactant proteins and lipids, and complement components are significantly altered in the aged lung in both mice and humans. Further, we show that the aging lung is a relatively oxidized environment. Our study provides new information on how the pulmonary environment in old age can potentially modify mucosal immune responses, thereby impacting pulmonary infections and other pulmonary diseases in the elderly population.

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“…В популяционном когортном исследова-нии выявлено, что более высокие уровни SP-D в системном кро-вотоке ассоциировались с повышенным уровнем смертности у пожилых женщин [65]. Другие исследователи утверждают, что уровень SP-D в сыворотке крови связан с сердечно-сосудистыми заболеваниями и общей смертностью у больных с ангиографиче-ски подтвержденным диагнозом ишемической болезни сердца независимо от других хорошо известных факторов риска (таких как возраст, курение, повышенный уровень холестерина и С-реактивного белка) [66,67].…”

Section: терапевтический архив 1 2015unclassified