Increased lungkine and chitinase levels in allergic airway inflammation: A proteomics approach

Zhao, Jing; Zhu, Hua; Wong, Chui Hong; Leung, Ka Yin; Wong, W.S. Fred

doi:10.1002/pmic.200401169

Cited by 82 publications

(67 citation statements)

References 48 publications

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“…on May 11, 2018 by guest http://iai.asm.org/ (80), were also found to be upregulated in the lungs of N. brasiliensis-infected WT and SCID mice (Table 1). Of particular note, transcription of gob-5 was significantly elevated through day 12 p.i.…”

Section: Vol 74 2006 Innate Immune Responses To Nippostrongylus 4973mentioning

confidence: 92%

Innate Immune Responses to Lung-Stage Helminth Infection Induce Alternatively Activated Alveolar Macrophages

2006

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While it is well established that infection with the rodent hookworm Nippostrongylus brasiliensis induces a strongly polarized Th2 immune response, little is known about the innate host-parasite interactions that lead to the development of this robust Th2 immunity. We exploited the transient pulmonary phase of N. brasiliensis development to study the innate immune responses induced by this helminth parasite in wild-type (WT) and severe-combined immune deficient (SCID) BALB/c mice. Histological analysis demonstrated that the cellular infiltrates caused by N. brasiliensis transit through the lungs were quickly resolved in WT mice but not in SCID mice. Microarray-based gene expression analysis demonstrated that there was a rapid induction of genes encoding molecules that participate in innate immunity and in repair/remodeling during days 2 to 4 postinfection in the lungs of WT and SCID mice. Of particular note was the rapid upregulation in both WT and SCID mice of the genes encoding YM1, FIZZ1, and Arg1, indicating a role for alternatively activated macrophages (AAMs) in pulmonary innate immunity. Immunohistochemistry revealed that nearly all alveolar macrophages became YM1-producing AAMs as early as day 2 postinfection. While the innate responses induced during the lung phase of N. brasiliensis infection were similar in complexity and magnitude in WT and SCID mice, only mice with functional T cells were capable of maintaining elevated levels of gene expression beyond the innate window of reactivity. The induction of alternatively activated alveolar macrophages could be important for dampening the level of inflammation in the lungs and contribute to the long-term decrease in pulmonary inflammation that has been associated with helminth infections.The cells and molecules that comprise the innate immune responses are the first line of defense against invading pathogenic organisms. In addition, innate immune mechanisms are important for the elimination of the myriad of nonpathogenic substances to which we are continuously exposed. In those circumstances in which the effector mechanisms of the innate response are not sufficient to fully eliminate a pathogen challenge, the same cells and molecules function to efficiently activate the antigen-specific adaptive arm of the immune response. In recent years, it has become clear that different modes of activation of innate immunity have a profound influence on the magnitude and the nature of subsequent adaptive responses (9,32,69).Parasitic nematodes are among the strongest natural inducers of polarized Th2 immune responses (2, 40, 60). Infection of mice with the intestinal nematode parasite Nippostrongylus brasiliensis has been used extensively to study the regulation of immunoglobulin E synthesis (31) and Th2 immunity in general (19,33). Despite the longstanding use of N. brasiliensis as a model, little is known about the innate immune responses that precede the induction of a highly polarized adaptive Th2 response to N. brasiliensis challenge. Indeed, there are only limite...

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Section: Vol 74 2006 Innate Immune Responses To Nippostrongylus 4973mentioning

confidence: 92%

Innate Immune Responses to Lung-Stage Helminth Infection Induce Alternatively Activated Alveolar Macrophages

2006

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“…One example in this respect is Ym1. This protein has been extensively studied since it is secreted by alternatively activated macrophages in mice under a variety of inflammatory conditions Welch et al 2002;Zhao et al 2005;Iwashita et al 2006;Reese et al 2007). The implications for human pathology, however, may be considered limited since no true human ortholog of Ym1 exists.…”

Section: Discussionmentioning

confidence: 99%

Evolution of Mammalian Chitinase(-Like) Members of Family 18 Glycosyl Hydrolases

et al. 2007

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Family 18 of glycosyl hydrolases encompasses chitinases and so-called chi-lectins lacking enzymatic activity due to amino acid substitutions in their active site. Both types of proteins widely occur in mammals although these organisms lack endogenous chitin. Their physiological function(s) as well as evolutionary relationships are still largely enigmatic. An overview of all family members is presented and their relationships are described. Molecular phylogenetic analyses suggest that both active chitinases (chitotriosidase and AMCase) result from an early gene duplication event. Further duplication events, followed by mutations leading to loss of chitinase activity, allowed evolution of the chi-lectins. The homologous genes encoding chitinase(-like) proteins are clustered in two distinct loci that display a high degree of synteny among mammals. Despite the shared chromosomal location and high homology, individual genes have evolved independently. Orthologs are more closely related than paralogues, and calculated substitution rate ratios indicate that protein-coding sequences underwent purifying selection. Substantial gene specialization has occurred in time, allowing for tissue-specific expression of pH optimized chitinases and chilectins. Finally, several family 18 chitinase-like proteins are present only in certain lineages of mammals, exemplifying recent evolutionary events in the chitinase protein family.

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“…Interestingly, elevated levels of chitinase-3-like proteins (Fig. 2) have been associated in humans and rodents with asthma and pulmonary allergic responses (34,35,60,61).…”

Section: Discussionmentioning

confidence: 99%

Loss of ABCG1 Results in Chronic Pulmonary Inflammation

Baldán

Gomes²,

Ping³

et al. 2008

The Journal of Immunology

117

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ABCG1, a member of the ATP-binding cassette transporter superfamily, is highly expressed in multiple cells of the lung. Loss of ABCG1 results in severe pulmonary lipidosis in mice, with massive deposition of cholesterol in both alveolar macrophages and type 2 cells and the accumulation of excessive surfactant phospholipids. These observations are consistent with ABCG1 controlling cellular sterol metabolism. Herein, we report on the progressive and chronic inflammatory process that accompanies the lipidosis in the lungs of Abcg1−/− mice. Compared with wild-type animals, the lungs of aged chow-fed mice deficient in ABCG1 show distinctive signs of inflammation that include macrophage accumulation, lymphocytic infiltration, hemorrhage, eosinophilic crystals, and elevated levels of numerous cytokines and cytokine receptors. Analysis of bronchoalveolar lavages obtained from Abcg1−/− mice revealed elevated numbers of foamy macrophages and leukocytes and the presence of multiple markers of inflammation including crystals of chitinase-3-like proteins. These data suggest that cholesterol and/or cholesterol metabolites that accumulate in Abcg1−/− lungs can trigger inflammatory signaling pathways. Consistent with this hypothesis, the expression of a number of cytokines was found to be significantly increased following increased cholesterol delivery to either primary peritoneal macrophages or Raw264.7 cells. Finally, cholesterol loading of primary mouse macrophages induced cytokine mRNAs to higher levels in Abcg1−/−, as compared with wild-type cells. These results demonstrate that ABCG1 plays critical roles in pulmonary homeostasis, balancing both lipid/cholesterol metabolism and inflammatory responses.

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Increased lungkine and chitinase levels in allergic airway inflammation: A proteomics approach

Cited by 82 publications

References 48 publications

Innate Immune Responses to Lung-Stage Helminth Infection Induce Alternatively Activated Alveolar Macrophages

Innate Immune Responses to Lung-Stage Helminth Infection Induce Alternatively Activated Alveolar Macrophages

Evolution of Mammalian Chitinase(-Like) Members of Family 18 Glycosyl Hydrolases

Loss of ABCG1 Results in Chronic Pulmonary Inflammation

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