Eotaxin Represents the Principal Eosinophil Chemoattractant in a Novel Murine Asthma Model Induced by House Dust Containing Cockroach Allergens

Kim, Jiyoun; Merry, Andrew; Nemzek, Jean A.; Bolgos, G.; Siddiqui, Javed; Remick, Daniel G.

doi:10.4049/jimmunol.167.5.2808

Cited by 51 publications

(74 citation statements)

References 43 publications

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“…The present study showed that there were increased levels of both eotaxins-1 and -2 in BAL fluid, suggesting that they may play a prominent role in children suffering from this disease. In a novel murine asthma model induced by house dust containing cockroach allergen, eotaxin-1 was found to represent the principal eosinophil attractant [32]. Indeed, in this latter study, neutralisation of eotaxin-1 with an antieotaxin-1 antibody inhibited airway eosinophilia following allergen challenge, suggesting that eotaxin-1 may be responsible for the pulmonary infiltration of eosinophils in response to cockroach allergen.…”

Section: Discussionmentioning

confidence: 63%

Role of the chemokines RANTES, monocyte chemotactic proteins-3 and -4, and eotaxins-1 and -2 in childhood asthma

Rojas‐Ramos¹,

Avalos²,

Pérez-Fernandez³

et al. 2003

European Respiratory Journal

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Eosinophil recruitment into the airways is a feature of asthma in children. However, the mechanisms by which these cells migrate into the airways are not fully understood. The present study investigated the presence of the eosinophilactivating chemokines regulated on activation, normal T-cell expressed and secreted (RANTES), monocyte chemotactic proteins (MCP)-3 and -4, and eotaxins-1 and -2 in the bronchoalveolar lavage (BAL) fluid obtained from both asthmatic (n=10, age 6-10 yrs) and normal children (n=10, age 5-10 yrs).Measurements of chemokines in BAL fluid showed that levels of RANTES, MCPs-3 and -4, and eotaxins-1 and -2 were significantly increased in fluid obtained from asthmatic children when compared with normal children. Among the different chemokines, RANTES was the cytokine released in greatest quantities in BAL fluid from asthmatic children. There was a significant correlation between the concentrations of MCP-4 and eosinophil numbers in BAL fluid and a trend between both chemokines MCP-3 and eotaxin-2 and eosinophils.Interestingly, the levels of most chemokines correlated with one another. These findings suggest that RANTES monocyte chemotactic proteins-3 and -4, and eotaxins-1 and -2 may regulate eosinophil trafficking into the airways of asthmatic children in a coordinated manner. Eur Respir J 2003; 22: 310-316.

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Section: Discussionmentioning

confidence: 63%

Role of the chemokines RANTES, monocyte chemotactic proteins-3 and -4, and eotaxins-1 and -2 in childhood asthma

Rojas‐Ramos¹,

Avalos²,

Pérez-Fernandez³

et al. 2003

European Respiratory Journal

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“…Each trauma group was challenged 48 hours after injury with 0.5 to 1.0 Â 10 8 CFU of Pseudomonas intratracheally using a well-described nonsurgical model. 19,20 Figure 4 Substance P (SP) levels in naive mice or 30 minutes after tail trauma or mTBI. Mice were subjected to tail trauma or mild traumatic brain injury (mTBI) and sacrificed 30 minutes later, naive mice had no manipulation.…”

Section: Mtbi Specifically Enhances Resistance To Pneumoniamentioning

confidence: 99%

The Role of Substance P in Pulmonary Clearance of Bacteria in Comparative Injury Models

Hsieh

Vaickus

Stein

et al. 2016

The American Journal of Pathology

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Neural input to the immune system can alter its ability to clear pathogens effectively. Patients suffering mild traumatic brain injury (mTBI) have shown reduced rates of pneumonia and a murine model replicated these findings, with better overall survival of TBI mice compared with sham-injured mice. To further investigate the mechanism of improved host response in TBI mice, this study developed and characterized a mild tail trauma model of similar severity to mild TBI. Both mild tail trauma and TBI induced similar systemic changes that normalized within 48 hours, including release of substance P. Examination of tissues showed that injuries are limited to the target tissue (ie, tail in tail trauma, brain in mTBI). Pneumonia challenge showed that mild TBI mice showed improved immune responses, characterized by the following: i) increased survival, ii) increased pulmonary neutrophil recruitment, iii) increased bacterial clearance, and iv) increased phagocytic cell killing of bacteria compared with tail trauma. Administration of a neurokinin-1ereceptor antagonist to block substance P signaling eliminated the improved survival of mTBI mice. Neurokinin-1ereceptor antagonism did not alter pneumonia mortality in tail trauma mice. These data show that immune benefits of trauma are specific to mTBI and that tail trauma is an appropriate control for future studies aimed at elucidating the mechanisms of improved innate immune responses in mTBI mice. Neural input exerts significant control on the ability of the immune system to clear pathogens effectively. Early studies have shown that stress has a profound detrimental effect on the immune response. 1 Psychologic or physiologic stress can result in dysregulation of these pathways, such as chronic activation, which ultimately leads to immunosuppression. 2 Activation of the vagus nerve also has been shown to induce powerful anti-inflammatory effects through the a7 nicotinic acetylcholine receptor. In severe traumatic brain injury (TBI) patients, it has been proposed that hyperactivity of the vagus depresses immune responses through strong dampening of proinflammatory mediator production. 3 In contrast to these studies showing that the neuroimmune axis decreases immune responses, our previous work documented that head trauma patients showed significantly reduced rates of pneumonia compared with blunt trauma patients. 4 A murine model of mild traumatic brain injury (mTBI) was able to reproduce these findings with enhanced resistance to bacterial pneumonia compared with sham injury mice. 4 mTBI mice showed improved survival, augmented pulmonary neutrophil recruitment, and reduced bacterial burdens compared with sham-injured mice. These findings show that neuroimmune modulation can show beneficial effects by improving immune function. Further investigation into the mechanisms by which mTBI augments the innate immune response could offer valuable insight into fighting infections in today's increasingly

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“…The syntenic region in humans, chromosome 17, has also been linked to asthma susceptibility. Eotaxin is responsible for the selective migration of eosinophils to the airways [11]. The effects are mediated via the chemokine receptor 3 (CCR3).…”

Section: Genetic Linkage To Atopy-related Phenotypes Of the Respiratomentioning

confidence: 99%

Mouse Models for the Genetic Dissection of Atopy

Heinzmann

Daser

2002

Int Arch Allergy Immunol

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Atopic disorders are complex traits with a significant contribution of heritability. Several mouse models for atopic phenotypes such as allergen-induced and intrinsic asthma, atopic dermatitis and immediate cutaneous hypersensitivity have been used to systematically dissect the genetics of these diseases. Many of the chromosomal regions identified in genome-wide screens colocalize with linkage regions of autoimmune phenotypes suggesting common regulatory genes in combination (or addition) to disease-specific genes. Moreover, many of these regions correspond to regions found in the human system, thus strengthening the likelihood of a gene contributing to the phenotype. The role of individual candidate genes has been vigorously pursued in genetically modified mice by destruction or overexpression of the candidate gene. The complex interactions of multiple contributing genes may further be elucidated in randomly mutated mouse strains. Thus mouse models can contribute largely to the elucidation of disease genes.

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Eotaxin Represents the Principal Eosinophil Chemoattractant in a Novel Murine Asthma Model Induced by House Dust Containing Cockroach Allergens

Cited by 51 publications

References 43 publications

Role of the chemokines RANTES, monocyte chemotactic proteins-3 and -4, and eotaxins-1 and -2 in childhood asthma

Role of the chemokines RANTES, monocyte chemotactic proteins-3 and -4, and eotaxins-1 and -2 in childhood asthma

The Role of Substance P in Pulmonary Clearance of Bacteria in Comparative Injury Models

Mouse Models for the Genetic Dissection of Atopy

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