Biomedical subjects

G Gauvreau

Publications and source records attributed to G Gauvreau.

3 recordsLinked to original sources

PubMed2001

Differences in functional consequences and signal transduction induced by IL-3, IL-5, and nerve growth factor in human basophils.

Previous studies have indicated a redundancy in the effects of the cytokines, IL-3, IL-5, and nerve growth factor (NGF) on acute priming of human basophils. In the current study, we have examined the effects of these three cytokines on 18-h priming for leukotriene C4 generation, their ability to induce Fc(epsilon)RIbeta mRNA expression, or their ability to sustain basophil viability in culture. We also examine a variety of the signaling steps that accompany activation with these cytokines. In contrast with the ability of IL-3 to alter secretagogue-mediated cytosolic calcium responses following 18-h cultures, 18-h treatment with IL-5 or NGF did not affect C5a-induced leukotriene C4 generation or alter C5a-induced intracellular Ca2+ concentration elevations. IL-3 and IL-5, but not NGF, induced Fc(epsilon)RIbeta mRNA expression and all three improved basophil viability in culture with a ranking of IL-3 > IL-5 > or = NGF. All three cytokines acutely activated the extracellular signal-regulated kinase pathway and the signaling elements that preceded extracellular signal-regulated kinase and cytosolic phospholipase A2 phosphorylation, consistent with their redundant ability to acutely prime basophils. However, only IL-3 and IL-5 induced Janus kinase 2 and STAT5 phosphorylation. This pattern of signal element activation among the three cytokines most closely matched their ability to induce expression of Fc(epsilon)RIbeta mRNA. Induction of the sustained calcium signaling that follows overnight priming with IL-3 appeared to be related to the strength of the early signals activated by these cytokines but the relevant pathway required was not identified. None of the signaling patterns matched the ability of the cytokines to promote basophil survival.

Adjuvants, Immunologic↗

PubMed1997

Bone marrow contribution to eosinophilic inflammation.

Allergen-induced bone marrow responses are observable in human allergic asthmatics, involving specific increases in eosinophil-basophil progenitors (Eo/B-CFU), measured either by hemopoietic assays or by flow cytometric analyses of CD34-positive, IL-3R alpha-positive, and/or IL-5-responsive cell populations. The results are consistent with the upregulation of an IL-5-sensitive population of progenitors in allergen-induced late phase asthmatic responses. Studies in vitro on the phenotype of developing eosinophils and basophils suggest that the early acquisition of IL-5R alpha, as well as the capacity to produce cytokines such as GM-CSF and IL-5, are features of the differentiation process. These observations are consistent with findings in animal models, indicating that allergen-induced increases in bone marrow progenitor formation depend on hemopoietic factor(s) released post-allergen. The possibility that there is constitutive marrow upregulation of eosinophilopoiesis in allergic airways disease is also an area for future investigation.

Allergens↗

PubMedDate not supplied

Regulation of IL-5 and IL-5 receptor expression in the bone marrow of allergic asthmatics.

BACKGROUND: Following consistent demonstrations of the clinical relevance of fluctuations in eosinophil-basophil (Eo-B) progenitors in the blood of patients with a variety of allergic airway disorders, we have turned our attention recently to hemopoietic events occurring in the bone marrow of allergic asthmatic subjects, utilizing a model of airway allergen challenge. METHODS: Flow-cytometric analyses of CD34/45+ progenitors for coexpression of surface alpha-receptor subunits for IL-3, IL-5 and GM-CSF, as well as in situ hybridization and in situ PCR methodologies to detect mRNA for IL-5 and GM-CSF in developing Eo-B in colony and liquid culture assays were employed before and after in vivo allergen challenge. RESULTS: An early, specific upregulation of IL-5R alpha expression on CD34/45 progenitors was observed after allergen challenge, concomitant with the development of the late-phase asthmatic response. Protein and mRNA for both GM-CSF and IL-5 were expressed in a time-dependent manner ex vivo, in developing (beta 7-integrin-positive), colony-derived Eo-B after allergen challenge in vivo. Both retinoic acid and corticosteroids were able to downregulate IL-3- and IL-5-induced expression of IL-5R on cord-blood-derived as well as HL-60 cloned Eo-B progenitors. CONCLUSION: These studies indicate the critical involvement of IL-5 and IL-5R in the induction of Eo-B differentiation and eosinophilic airway inflammation in allergic asthmatics, and point to these events as potential targets for long-term therapy of atopic disease.

Asthma↗