Mast Cell-Specific Deletion of Group III Secreted Phospholipase A 2 Impairs Mast Cell Maturation and Functions

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 A (sPLA -III) released from immature MCs is functionally coupled with lipocalin-type prostaglandin D (PGD ) synthase in neighboring fibroblasts to supply a microenvironmental pool of PGD , which in turn acts on the PGD receptor DP1 on MCs to promote their proper maturation. In the present study, we reevaluated the role of sPLA -III in MCs using a newly generated MC-specific -deficient mouse strain. Mice lacking sPLA -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 -deficient mice, as well as MC-deficient mice reconstituted with MCs prepared from global null mice, displayed a significant reduction in irritant contact dermatitis (ICD) and an aggravation of contact hypersensitivity (CHS). The increased CHS response by deficiency depended at least partly on the reduced expression of hematopoietic PGD synthase and thereby reduced production of PGD due to immaturity of MCs. Overall, our present study has confirmed that MC-secreted sPLA -III promotes MC maturation, thereby facilitating acute anaphylactic and ICD reactions and limiting delayed CHS response.