Fig. 4.

Properties and functions of sPLA₂-III. (A) The role of sPLA₂-III in mast cell maturation and allergy [34]. sPLA₂-III is released from immature mast cells and coupled with fibroblastic L-PGDS to produce a microenvironmental pool of PGD₂, which in turn acts on DP1 to promote mast cell maturation. Mature mast cells, which express cPLA₂α and hematopoietic PGD₂ synthase (H-PGDS) abundantly, release a distinct pool of PGD₂ as well as histamine following activation by IgE and antigen, leading to allergic responses. Disturbance of the paracrine sPLA₂-III-L-PGDS-DP1 circuit hampers the maturation and thereby activation of mast cells, resulting in impairment of allergic responses. (B) The roles of distinct PLA₂s in the colon [44,92]. cPLA₂α releases a pool of AA that is converted to PGH₂ by cyclooxygenase-2 (COX-2) and then to PGE₂ by microsomal PGE₂ synthase (mPGES-1). This cPLA₂α-driven PGE₂ confers protection from colitis through its receptor EP4 [143]. sPLA₂-X releases ω3 EPA/DHA, which blocks harmful Th17 responses in colitis through the PUFA receptor GPR120. In contrast, sPLA₂-III supplies lysophospholipids such as LPA and LPI, which promote colitis and colorectal cancer probably through their receptors LPA₂ and GPR55, respectively. Representative images of the colons of WT, Pla2g4a^−/− and Pla2g10^−/− mice treated with 1% DSS and those of Pla2g3^+/+ and Pla2g3^−/− mice treated with 1.5% DSS are shown. (C) Real-time PCR of Pla2g3 mRNA in the brain of 8-week-old C57BL/6 mice (n = 4, mean ± SEM). These results agree with a previous report [125]. (D) In situ hybridization of Pla2g3 mRNA in the brain of newborn C57BL/6 mice. Signals for Pla2g3 mRNA (blue) are located in several neurons within the hypothalamus and brainstem.