Mast cells express IL‐13R<i>α</i>1: IL‐13 promotes human lung mast cell proliferation and Fc<i>ɛ</i>RI expression

Kaur, Davinder; Hollins, Fay; Woodman, Lucy; Yang, Weidong; Monk, Phillip; May, Richard; Bradding, Peter; Brightling, Christopher E.

doi:10.1111/j.1398-9995.2006.01139.x

Cited by 77 publications

(64 citation statements)

References 32 publications

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“…Early therapeutic potential of CAT-354 for asthma was demonstrated by Blanchard et al via a murine model in which CAT-354 significantly inhibited IL-13-induced AHR and airway eosinophilia [14]. Kaur et al demonstrated that human lung mast cells (HLMCs) expressed IL-13, that IL-13 can up-regulate allergic functions of HLMCs and, specifically, that CAT-354 inhibited all of these IL-13-mediated effects in HLMCs [15].…”

Section: Discussionmentioning

confidence: 99%

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An open‐label, single‐dose bioavailability study of the pharmacokinetics of CAT‐354 after subcutaneous and intravenous administration in healthy males

Oh¹,

Faggioni²,

Jin³

et al. 2010

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• The safety profile and effective dose of CAT-354 have been determined with intravenous (i.v.) administration, but no information is available on subcutaneous (s.c.) administration. WHAT THIS STUDY ADDS• This study characterized the pharmacokinetics of CAT-354 following s.c. administration of 150 mg and 300 mg doses, and indicated a bioavailability of approximately 60%. AIMTo assess the bioavailability and pharmacokinetics of CAT-354, an anti-IL-13 human monoclonal IgG4 antibody, following subcutaneous (s.c.) and intravenous (i.v.) administration. METHODSThis was a single-dose, randomized, open-label, parallel-group bioavailability study. Healthy male subjects aged 20-54 years were randomly assigned to one of three dose groups (n = 10/group) to receive CAT-354: 150 mg i.v.; 150 mg s.c. or 300 mg s.c. (two 150 mg injections). Serum pharmacokinetics, adverse events (AEs), vital signs, electrocardiograms and laboratory parameters were assessed. RESULTSCAT-354 showed bioavailability of 62% and 60% after 150 mg and 300 mg s.c. doses, respectively, and linear pharmacokinetics over the dose range tested. Peak serum concentrations in the s.c. groups occurred after 3-9 (median 5) days, with a mean elimination half-life of 19.2 Ϯ 3.1 days (150 mg) and 19.4 Ϯ 3.59 days (300 mg) after s.c. and 21.4 Ϯ 2.46 days after i.v. administration. Volume of distribution at steady state (Vss) was 4960 Ϯ 1440 ml kg -1 after i.v. (slightly greater than plasma volume). Average apparent clearances (CL/F) were 292 Ϯ 82.3 and 307 Ϯ 109 ml day -1 after 150 and 300 mg s.c., respectively; systemic CL of 188 Ϯ 84.0 ml day -1 after i.v. dosing was consistent with endogenous IgG and reticuloendothelial elimination. No severe or serious AEs occurred. Among 40 reported AEs, 25 were headache, sinus disorders/respiratory symptoms and changes in body temperature perception. CONCLUSIONSCAT-354 exhibited bioavailability of approximately 60% when given s.c. to healthy male subjects.

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Section: Discussionmentioning

confidence: 99%

“…CAT-354 is a human monoclonal IgG4 antibody which has been shown to neutralize IL-13 in both the murine airway [14] and human lung mast cells [15]. Phase 1 data in subjects with mild-to-moderate asthma have demonstrated safety and tolerability profiles that support continued clinical development of CAT-354 [16].…”

Section: Introductionmentioning

confidence: 99%

An open‐label, single‐dose bioavailability study of the pharmacokinetics of CAT‐354 after subcutaneous and intravenous administration in healthy males

Oh¹,

Faggioni²,

Jin³

et al. 2010

Brit J Clinical Pharma

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“…[22][23][24][25] IL-13 is also known to promote mast cell proliferation. 16,26 IL-13 is produced by Th2 lymphocytes and activated mast cells and is implicated in the immunopathogenesis of various allergic diseases. 16,26,27 The relationship between mast cell infiltration and the histological subtype of CHL (NSCHL or non-NSCHL) remains controversial.…”

Section: Discussionmentioning

confidence: 99%

“…12 Mast cell proliferation is induced by IL-3, IL-13, and stem cell factor (SCF). [13][14][15][16] We investigated the association of fibrosis in lymph nodes (LNs) of patients with CHL through histological examination of the expression of cytokines associated with fibrosis and mast cell proliferation (TGF-β, IL-3, IL-13, and SCF) and by determining the degree of mast cell infiltration in NSCHL compared with that in non-NSCHL (MCCHL or LRCHL).…”

Section: Introductionmentioning

confidence: 99%

Role of mast cells in fibrosis of classical Hodgkin lymphoma

Nakayama

Yokote

Hiraoka

et al. 2016

Int J Immunopathol Pharmacol

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The underlying mechanism of fibrosis in classical Hodgkin lymphoma (CHL) remains uncertain. This study aimed to investigate the association of fibrosis in the lymph nodes of patients with CHL through histological examination of the expression of cytokines associated with fibrosis and mast cell proliferation. Additionally, we sought to determine the degree of mast cell infiltration in a nodular sclerosis subtype of CHL (NSCHL) compared with that in non-NSCHL. We analyzed lymph nodes from 22 patients with CHL, of which eight were of the NSCHL and 14 of the non-NSCHL subtype, using immunohistochemical staining of forkhead box P3 (FOXP3), transforming growth factor (TGF)-β, interleukin (IL)-3, IL-13, and stem cell factor (SCF). Mast cells were positive for TGF-β and IL-13, and FOXP3-positive cells were negative for TGF-β. Only the expression of IL-13 in Hodgkin and Reed-Sternberg (HRS) cells was significantly more frequently observed in NSCHL than that in non-NSCHL (P = 0.0028) and was associated with a higher rate of fibrosis (P = 0.0097). The number of mast cells was significantly higher in NSCHL than that in non-NSCHL (P = 0.0001). A significantly positive correlation was observed between the rate of fibrosis and the number of mast cells (correlation coefficient, 0.8524; 95% CI, 0.6725-0.9372) (P <0.0001). The number of mast cells was significantly higher in the group with IL-13-positive HRS cells than that in the group with IL-13-negative HRS cells (P = 0.0157). Based on these findings, we hypothesize that IL-13 production by HRS cells may lead to fibrosis, and furthermore, promote mast cell proliferation and infiltration. This in turn might further produce the fibrotic cytokines IL-13 and TGF-β, resulting in fibrosis typical of NSCHL.

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“…The accumulated data have led to the conclusion that IL13R␣2 functions in most cell types as a critical decoy/inhibitory receptor for IL-13-dependent activation of cells. Kaur and coworkers (56) showed that in vivo-differentiated MCs from human lung also express IL13R␣1, and Lorentz and coworkers (57) showed that normal human intestinal MCs express both IL13R␣1 and IL13R␣2. Not only do canine MC lines express IL13R␣1 and IL13R␣2, the transcript that encodes canine IL13R␣2 was first cloned from a mastocytoma cell line (58).…”

Section: Discussionmentioning

confidence: 99%

The Diacylglycerol-dependent Translocation of Ras Guanine Nucleotide-releasing Protein 4 inside a Human Mast Cell Line Results in Substantial Phenotypic Changes, Including Expression of Interleukin 13 Receptor α2

Katsoulotos

Miao

et al. 2008

Journal of Biological Chemistry

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(2) is abundantly expressed in T cells where it facilitates T-cell receptor-Ras signaling (3, 4). RasGRP1 is required for the final stages of T-cell development, and mice lacking this signaling protein develop a lymphoproliferative autoimmune disorder that resembles that seen in patients with systemic lupus erythematosus (5). Dysregulation of RasGRP1 expression also is the eighth leading cause of retroviral induced B-and T-cell leukemia in mice (6, 7). RasGRP3 (8, 9) is more abundant in B cells where it facilitates B-cell receptor-Ras signaling, and RasGRP3-null mice have low levels of IgG2a (10, 11). RasGRP2 (12-14) is expressed in megakaryocytes and platelets, and targeted disruption of its gene results in defective integrin-dependent signaling in these cells (15).Culture of mouse bone marrow cells for 3 weeks in the presence of interleukin (IL) 3 results in a population of immature cells (16) (designated as mBMMCs) that can give rise to all known populations of tissue mast cells (MCs) when adoptively transferred into MC-deficient WBB6F 1 -W/W v mice (17-19). Sequence analysis of thousands of arbitrarily selected cDNAs from a BALB/c mBMMC cDNA library resulted in the cloning of the 2.3-kb cDNA and 19-kb/18-exon gene that encode mouse RasGRP4 (mRasGRP4) (20). Using homology-based screening approaches, the corresponding cDNAs and genes * This work was supported in part by a National Health and Medical Research Council (NHMRC) (Australia) Project Grant (to S. A. K.) and by National Institutes of Health Grants AI-54950 and HL-36110 (to R. L. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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Mast cells express IL‐13Rα1: IL‐13 promotes human lung mast cell proliferation and FcɛRI expression

Cited by 77 publications

References 32 publications

An open‐label, single‐dose bioavailability study of the pharmacokinetics of CAT‐354 after subcutaneous and intravenous administration in healthy males

An open‐label, single‐dose bioavailability study of the pharmacokinetics of CAT‐354 after subcutaneous and intravenous administration in healthy males

Role of mast cells in fibrosis of classical Hodgkin lymphoma

The Diacylglycerol-dependent Translocation of Ras Guanine Nucleotide-releasing Protein 4 inside a Human Mast Cell Line Results in Substantial Phenotypic Changes, Including Expression of Interleukin 13 Receptor α2

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