422923

Upregulation of Mast Cells Degranulation and Anaphylaxis Biomarkers via Substance P and Calcium Ionophore: Possible implication in Extracellular Allergic Disease

Article

Last updated: 27 Apr 2025

Subjects

-

Tags

Biochemistry and Molecular Biology

Abstract

Background: Mast cells play crucial roles in the pathogenesis of allergies through the secretion of powerful mediators, prominent among which is a group of proteases that are stored and function within the intracellular granules of mast cells.
Objectives: We aimed to investigate the secretion of these proteases from mast cells during degranulation and to explore the factors that can influence the secretion and gene expression of mast cell mediators.
Materials and methods: Mast cell line (LAD2) were stimulated to degranulate with calcium ionophore A23187 (CaI) or substance P (SP).  Gene expressions of dipeptidyl peptidase I (DPPI) and carboxypeptidase A3 (CPA3), chymase (CHY), tryptase (TRY) were determined by quantitative RT-PCR.  Alterations in gene expression were investigated at time points ranging from 0.5 to 6 hours following cell stimulation. Beta-hexosaminidase activity and DPPI levels were measured using ELISA. 
Results: Experimental stimulation of sensitized mast cells by CaI or SP, revealed by the release of the activation marker β-hexosaminidase in a time dependent manner (net release=63% ± 2.4 at 6 h),  this was associated with significant increases in gene expression for DPPI and also for CPA3, CHY and TRY. Cal sensitization produced a significant increase in DPPI, CPA3 and CHY in the first 30m of stimulation with gradual decrease in levels with time but still significantly higher than non-stimulated cells (p≤0.05 for all). The reverse for TRY, as the most significant increase in its expression was at 2H. SP produced a gradual increase in gene expression for all studied parameters (p≤0.05 for all) with the most significant increase was for TRY gene at 2h (p˂0.01 vs cal).
Conclusion: DPPI can be released from mast cells on degranulation, and the subsequent increases in gene expression would be consistent with the later replenishment of secretory granules.  This protease may participate in processes of protease activation and other activities outside the cell in inflammatory disease. Thus, DPPI could be represented as an innovative marker for mast cell sensitization which may accurately diagnose the allergic responses specially when measured as panel with CPA3, CHY and TRY.

DOI

10.21608/svuijm.2025.373499.2159

Keywords

Degranulation, DPPI, inflammatory disease, mast cells, Proteases

Authors

First Name

Naglaa K.

Last Name

Idriss

MiddleName

-

Affiliation

Immunopharmacology Group, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD, UK, & Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Assiut University, Assiut, Egypt, & Department of Basic Medical Science, Badr University, New Naser City, West of Assiut, Assiut, Egypt

Email

naglaaidriss@hotmail.com

City

-

Orcid

-

First Name

Andrew F.

Last Name

Walls

MiddleName

-

Affiliation

Immunopharmacology Group, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD, UK.

Email

a.f.walls@soton.ac.uk

City

-

Orcid

-

First Name

Laurie C.

Last Name

Lau

MiddleName

-

Affiliation

Immunopharmacology Group, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD, UK.

Email

lcl@soton.ac.uk

City

-

Orcid

-

First Name

Mogib E.

Last Name

Khedr

MiddleName

-

Affiliation

Immunopharmacology Group, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD, UK.

Email

mek1y13@soton.ac.uk

City

-

Orcid

-

First Name

Rana S.

Last Name

Abadalkareem

MiddleName

-

Affiliation

Immunopharmacology Group, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD, UK.

Email

ra2e19@soton.ac.uk

City

-

Orcid

-

First Name

Reham I.

Last Name

El-Mahdy

MiddleName

-

Affiliation

Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Assiut University, Assiut, Egypt, & Department of Basic Medical Science, Badr University, New Naser City, West of Assiut, Assiut, Egypt.

Email

rehambio@yahoo.com

City

-

Orcid

-

First Name

Amr

Last Name

Ashry

MiddleName

-

Affiliation

Department of Cardiothoracic Surgery, Assiut University Hospital, Faculty of Medicine, Assiut University, Assiut, Egypt

Email

amrashry@hotmail.com

City

-

Orcid

-

First Name

Marwa A.

Last Name

Gaber

MiddleName

-

Affiliation

Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Assiut University, Assiut, Egypt, & Biochemistry Department, Sphinx University, New Assiut, Egypt

Email

marwagaber@aun.edu.eg

City

-

Orcid

-

Volume

8

Article Issue

1

Related Issue

52988

Issue Date

2025-01-01

Receive Date

2025-04-12

Publish Date

2025-01-01

Page Start

852

Page End

865

Print ISSN

2735-427X

Online ISSN

2636-3402

Link

https://svuijm.journals.ekb.eg/article_422923.html

Detail API

http://journals.ekb.eg?_action=service&article_code=422923

Order

422,923

Type

Original research articles

Type Code

1,520

Publication Type

Journal

Publication Title

SVU-International Journal of Medical Sciences

Publication Link

https://svuijm.journals.ekb.eg/

MainTitle

Upregulation of Mast Cells Degranulation and Anaphylaxis Biomarkers via Substance P and Calcium Ionophore: Possible implication in Extracellular Allergic Disease

Details

Type

Article

Created At

27 Apr 2025