PMID- 37258146
OWN - NLM
STAT- MEDLINE
DCOM- 20230602
LR  - 20230602
IS  - 1347-5215 (Electronic)
IS  - 0918-6158 (Linking)
VI  - 46
IP  - 6
DP  - 2023
TI  - Ephedrine Alkaloid-Independent High-Affinity Immunoglobulin-E Receptor (FcepsilonRI) 
      Internalization Results in CCL2 Production without Inducing Mast Cell 
      Degranulation.
PG  - 811-816
LID - 10.1248/bpb.b23-00006 [doi]
AB  - Mast cells (MCs) play an important role in allergies, leading to the development 
      of MC-targeted therapies. Ephedra herb (Mao) has potent anti-allergic activity, 
      but contains ephedrine alkaloids (EAs); therefore, its hazardous effects are 
      taken into consideration during its clinical use. We previously reported that Mao 
      attenuates robust MC degranulation by an allergen through high-affinity 
      immunoglobulin E (IgE) receptor (FcepsilonRI) internalization, in which an 
      EA-independent mechanism was suggested to be at play. This study aimed to deepen 
      our understanding of the potential of Mao against FcepsilonRI internalization using two 
      strains with different EA contents. Mao extracts were administered to bone 
      marrow-derived MCs (BMMCs), and their cellular responses, including FcepsilonRI 
      internalization, were analyzed. In addition, physiological events were evaluated 
      using a passive cutaneous anaphylactic (PCA) reaction mouse model. BMMCs mediate 
      the production of diverse inflammatory mediators. Among these, the potent 
      chemokine CCL2 is thought to be differentially regulated from other 
      pro-inflammatory mediators. We found that Mao significantly induces CCL2 
      expression in BMMCs despite suppressing robust degranulation through FcepsilonRI 
      internalization. Importantly, this was a distinctly EAs-independent response. In 
      the PCA reaction, local MC activation following allergen challenge was suppressed 
      by Mao treatment, which strengthened the view that Mao sufficiently decreased the 
      rapid activation of MCs and promoted CCL2 secretion. Collectively, these 
      observations provide additional insights into the mechanism of Mao-induced silent 
      FcepsilonRI internalization in MCs and the complex and heterogeneous secretory 
      responses operating in MCs.
FAU - Nagata, Yuka
AU  - Nagata Y
AD  - Laboratory of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Institute 
      of Medical, Pharmaceutical and Health Sciences, Kanazawa University.
FAU - Sasaki, Yohei
AU  - Sasaki Y
AD  - Laboratory of Pharmacognosy, Faculty of Pharmaceutical Sciences, Institute of 
      Medical, Pharmaceutical and Health Sciences, Kanazawa University.
FAU - Suzuki, Ryo
AU  - Suzuki R
AD  - Laboratory of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Institute 
      of Medical, Pharmaceutical and Health Sciences, Kanazawa University.
LA  - eng
PT  - Journal Article
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (Receptors, IgE)
RN  - GN83C131XS (Ephedrine)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Alkaloids)
RN  - 0 (Allergens)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Immunoglobulins)
RN  - EC 1.4.3.4 (Monoamine Oxidase)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Receptors, IgE/metabolism
MH  - Ephedrine/metabolism
MH  - Cell Degranulation
MH  - Mast Cells/metabolism
MH  - *Antineoplastic Agents/pharmacology
MH  - *Alkaloids/pharmacology
MH  - Allergens/metabolism
MH  - Inflammation Mediators/metabolism
MH  - Immunoglobulins
MH  - Monoamine Oxidase/metabolism/pharmacology
OTO - NOTNLM
OT  - Mao
OT  - chemokine
OT  - ephedra herb
OT  - ephedrine alkaloid
OT  - mast cell
EDAT- 2023/06/01 01:08
MHDA- 2023/06/02 06:42
CRDT- 2023/05/31 21:38
PHST- 2023/06/02 06:42 [medline]
PHST- 2023/06/01 01:08 [pubmed]
PHST- 2023/05/31 21:38 [entrez]
AID - 10.1248/bpb.b23-00006 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2023;46(6):811-816. doi: 10.1248/bpb.b23-00006.