Complement levels and activity in the normal and LPS-injured lung

Bolger, Molly S.; Ross, De Andre S.; Jiang, Haixiang; Frank, Michael M.; Ghio, Andrew J.; Schwartz, David A.; Wright, Jo Rae

doi:10.1152/ajplung.00127.2006

Cited by 78 publications

(76 citation statements)

References 52 publications

(58 reference statements)

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“…Using TNF-a as an example, the network analysis showed that in addition to proinflammatory proteins, TNF-a interacted with bacterial opsonins (complement proteins, SFTPA), mediators of apoptosis (annexin A5, annexin A1), and proteins involved in lung repair (EGFR) (30)(31)(32). This suggests that TNF-a modulates pathways involved in innate immunity and repair in the lungs, in addition to inflammation.…”

Section: Discussionmentioning

confidence: 99%

Proteomic and Computational Analysis of Bronchoalveolar Proteins during the Course of the Acute Respiratory Distress Syndrome

Chang¹,

Hayashi²,

Gharib³

et al. 2008

Am J Respir Crit Care Med

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Rationale: Acute lung injury causes complex changes in protein expression in the lungs. Whereas most prior studies focused on single proteins, newer methods allowing the simultaneous study of many proteins could lead to a better understanding of pathogenesis and new targets for treatment. Objectives: The purpose of this study was to examine the changes in protein expression in the bronchoalveolar lavage fluid (BALF) of patients during the course of the acute respiratory distress syndrome (ARDS). Methods: Using two-dimensional difference gel electrophoresis (DIGE), the expression of proteins in the BALF from patients on Days 1 (n 5 7), 3 (n 5 8), and 7 (n 5 5) of ARDS were compared with findings in normal volunteers (n 5 9). The patterns of protein expression were analyzed using principal component analysis (PCA). Biological processes that were enriched in the BALF proteins of patients with ARDS were identified using Gene Ontology (GO) analysis. Protein networks that model the protein interactions in the BALF were generated using Ingenuity Pathway Analysis. Measurements and Main Results: An average of 991 protein spots were detected using DIGE. Of these, 80 protein spots, representing 37 unique proteins in all of the fluids, were identified using mass spectrometry. PCA confirmed important differences between the proteins in the ARDS and normal samples. GO analysis showed that these differences are due to the enrichment of proteins involved in inflammation, infection, and injury. The protein network analysis showed that the protein interactions in ARDS are complex and redundant, and revealed unexpected central components in the protein networks. Conclusions: Proteomics and protein network analysis reveals the complex nature of lung protein interactions in ARDS. The results provide new insights about protein networks in injured lungs, and identify novel mediators that are likely to be involved in the pathogenesis and progression of acute lung injury.

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Section: Discussionmentioning

confidence: 99%

Proteomic and Computational Analysis of Bronchoalveolar Proteins during the Course of the Acute Respiratory Distress Syndrome

Chang¹,

Hayashi²,

Gharib³

et al. 2008

Am J Respir Crit Care Med

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“…Complement proteins (and their cleavage products) have been detected in human ALF obtained from healthy hosts, where complement levels differed from levels in human serum (Bolger et al 2007). Complement is a complex, highly regulated protein system with an essential role in host defense through bacterial lysis, stimulation of phagocytosis, recruitment of immune cells to infected/ damaged tissue, and promotion of the inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

“…Complement protein levels were determined in ALF-L from old and young mice and adult and elderly humans by Western blotting. We focused primarily on the classical complement pathway as we and others have shown that components of the alternative complement pathway are at very low levels in ALF (Bolger et al 2007;Ferguson et al 2004). C2, C3, and C4 molecules were determined.…”

Section: Alf Cytokines Are Altered In Old Agementioning

confidence: 99%

“…C2, C3, and C4 molecules were determined. For completeness, we also measured factor B (FB) of the alternative pathway and C5 and C7 molecules as indicators of an alteration in formation of the membrane attack complex (Bolger et al 2007). Old mice had significantly higher levels of complement proteins C3β, C4α (not shown) and C4β (both products of C4 cleavage), and FBα and FBβ (Fig.…”

Section: Alf Cytokines Are Altered In Old Agementioning

confidence: 99%

“…For human ALF, the following ABS w e r e u s e d : S P -A ( s c -1 6 6 9 1 4 , S a n t a C r u z Biotechnology, Inc.), SP-D (sc-59695, Santa Cruz Biotechnology, Inc.), C2 (sc-134639, Santa Cruz Biotechnology, Inc.), C3 (sc-28294/B9, Santa Cruz Biotechnology, Inc.), C5 (A220, Complement Technology, Inc., www.complementtech.com), and C7 (sc-160195, Santa Cruz Biotechnology, Inc.). Western blotting (WB) to detect SP-A, SP-D, and complement components and to determine the presence of nitrotyrosine and carbonyl residues were performed following the manufacturer's recommendations and established methods (Bolger et al 2007;Clay et al 2008). The carbonyl and nitrotyrosine presence was determined assessing the band density of all bands in the lane.…”

Section: Cytokine and Mpo Elisasmentioning

confidence: 99%

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Molecular composition of the alveolar lining fluid in the aging lung

Moliva

Rajaram

Sidiki

et al. 2014

AGE

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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The complement system in Aspergillus fumigatus infections and its crosstalk with pentraxins

et al. 2020

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Aspergillosis is a life-threatening infection mostly affecting immunocompromised individuals and primarily caused by the saprophytic fungus Aspergillus fumigatus. At the host-pathogen interface, both cellular and humoral components of the innate immune system are increasingly acknowledged as essential players in the recognition and disposal of this opportunistic mold. Fundamental hereof is the contribution of the complement system, which deploys all three activation pathways in the battle against A. fumigatus, and functionally cooperates with other soluble pattern recognition molecules, including pentraxins. In particular, preclinical and clinical observations point to the long pentraxin PTX3 as a nonredundant and complement-dependent effector with protective functions against A. fumigatus.Based on past and current literature, here we discuss how the complement participates in the immune response to this fungal pathogen, and illustrate its crosstalk with the pentraxins, with a focus on PTX3. Emphasis is placed on the molecular mechanisms underlying such processes, the genetic evidence from human epidemiology, and the translational potential of the currently available knowledge.Aspergillus fumigatus is an evolutionary ancient filamentous fungus (mold) that flourishes in soil and decomposing vegetation [1]. Traditionally regarded as asexual, the life cycle of this ubiquitous saprophyte actually comprises cryptic forms of sexual reproduction [2] and is hallmarked by several morphotypes with distinct metabolic, compositional, and structural traits [3]. The metabolically inactive and asexual airborne spores (known as dormant or resting conidia) are encased in a robust cell wall mostly made of complex polysaccharides [i.e., aand b-glucans, chitin, galactomannan (GM), and galactosaminogalactan (GAG)] in addition to lipids, proteins, and melanin pigments [i.e., dihydroxynaphthalene (DHN) melanin] [4]. Small in size (i.e., 2-3 µm across) and enveloped in a layer of hydrophobic rodlet-like proteins (i.e.

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Complement levels and activity in the normal and LPS-injured lung

Cited by 78 publications

References 52 publications

Proteomic and Computational Analysis of Bronchoalveolar Proteins during the Course of the Acute Respiratory Distress Syndrome

Proteomic and Computational Analysis of Bronchoalveolar Proteins during the Course of the Acute Respiratory Distress Syndrome

Molecular composition of the alveolar lining fluid in the aging lung

The complement system in Aspergillus fumigatus infections and its crosstalk with pentraxins

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