Targeting mast cells: Uncovering prolific therapeutic role in myriad diseases.
The mast cells are integral part of immune system and they have pleiotropic physiological functions in our body. Any type of abnormal stimuli causes the mast cells receptors to spur the otherwise innocuous mast cells to degranulate and release inflammatory mediators like histamine, cytokines, chemokines and prostaglandins. These mediators are involved in various diseases like allergy, asthma, mastocytosis, cardiovascular disorders, etc. Herein, we describe the receptors involved in degranulation of mast cells and are broadly divided into four categories: G-protein coupled receptors, ligand gated ion channels, immunoreceptors and pattern recognition receptors. Although, activation of pattern recognition receptors do not cause mast cell degranulation, but result in cytokines production. Degranulation itself is a complex process involving cascade of events like membrane fusion events and various proteins like VAMP, Syntaxins, DOCK5, SNAP-23, MARCKS. Furthermore, we described these mast cell receptors antagonists or agonists useful in treatment of myriad diseases. Like, omalizumab anti-IgE antibody is highly effective in asthma, allergic disorders treatment and recently mechanistic insight of IgE uncovered; matrix mettaloprotease inhibitor marimistat is under phase III trial for inflammation, muscular dystrophy diseases; ZPL-389 (H4 receptor antagonist) is in Phase 2a Clinical Trial for atopic dermatitis and psoriasis; JNJ3851868 an oral H4 receptor antagonist is in phase II clinical development for asthma, rheumatoid arthritis. Therefore, research is still in inchoate stage to uncover mast cell biology, mast cell receptors, their therapeutic role in myriad diseases.
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, Punjab, India.
Jatinder
J
Singh
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, Punjab, India.
Ramanpreet
R
Shah
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, Punjab, India. Electronic address: ddd300@gmail.com.
Dhandeep
D
Singh
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000628:therapy*; D015550:Cell Degranulation / Q000187:drug effects; D002986:Clinical Trials as Topic; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy*; D007167:Immunotherapy / Q000379:methods*; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D011565:Psoriasis / Q000276:immunology / Q000628:therapy*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4
D000893:Anti-Inflammatory Agents; D000888:Antibodies, Anti-Idiotypic; C418607:HRH4 protein, human; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; C026408:anti-IgE antibodies
Cytokine receptors; G-protein coupled receptors; Ligand gated ion channels; MRGPRX2; Mast cells