Mast Cell-Specific Deletion of Group III Secreted Phospholipase A2 Impairs Mast Cell Maturation and Functions.

Abstract

Tissue-resident mast cells (MCs) have important roles in IgE-associated and -independent allergic reactions. Although microenvironmental alterations in MC phenotypes affect the susceptibility to allergy, understanding of the regulation of MC maturation is still incomplete. We previously reported that group III secreted phospholipase A2 (sPLA2-III) released from immature MCs is functionally coupled with lipocalin-type prostaglandin D2 (PGD2) synthase in neighboring fibroblasts to supply a microenvironmental pool of PGD2, which in turn acts on the PGD2 receptor DP1 on MCs to promote their proper maturation. In the present study, we reevaluated the role of sPLA2-III in MCs using a newly generated MC-specific Pla2g3-deficient mouse strain. Mice lacking sPLA2-III specifically in MCs, like those lacking the enzyme in all tissues, had immature MCs and displayed reduced local and systemic anaphylactic responses. Furthermore, MC-specific Pla2g3-deficient mice, as well as MC-deficient KitW-sh mice reconstituted with MCs prepared from global Pla2g3-null mice, displayed a significant reduction in irritant contact dermatitis (ICD) and an aggravation of contact hypersensitivity (CHS). The increased CHS response by Pla2g3 deficiency depended at least partly on the reduced expression of hematopoietic PGD2 synthase and thereby reduced production of PGD2 due to immaturity of MCs. Overall, our present study has confirmed that MC-secreted sPLA2-III promotes MC maturation, thereby facilitating acute anaphylactic and ICD reactions and limiting delayed CHS response.

• Authors: Yoshitaka Taketomi, Yuki Endo, Takayoshi Higashi, Remi Murase, Tomio Ono, Choji Taya, Tetsuyuki Kobayashi, Makoto Murakami
• Journal: Cells (Cells) Vol. 10 Issue 7 (07 04 2021) ISSN: 2073-4409 [Electronic] Switzerland
• PMID: 34359862 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Phospholipases A2, Secretory

Topics

• Anaphylaxis (pathology)
• Animals
• Cell Differentiation
• Dermatitis (pathology)
• Dermatitis, Contact (pathology)
• Fibroblasts (pathology)
• Gene Deletion
• Mast Cells (enzymology, pathology)
• Mice, Inbred C57BL
• Phospholipases A2, Secretory (deficiency, metabolism)