SUBSTANCE-P-INDUCED AUGMENTATION OF CUTANEOUS VASCULAR-PERMEABILITY AND GRANULOCYTE INFILTRATION IN MICE IS MAST-CELL DEPENDENT
SUBSTANCE-P-INDUCED AUGMENTATION OF CUTANEOUS VASCULAR-PERMEABILITY AND GRANULOCYTE INFILTRATION IN MICE IS MAST-CELL DEPENDENT
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DOI：
10.1172/jci114295
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发表时间：
1989-10-01
影响因子：
15.9
通讯作者：
GALLI, SJ
中科院分区：
文献类型：
--
作者：
YANO, H;WERSHIL, BK;GALLI, SJ
十一肽P物质被认为当从皮肤中的感觉神经末梢释放时介导血管舒张和血管通透性增加。P物质在体外或体内也可诱导肥大细胞脱颗粒。然而，在何种程度上P物质诱导的血管通透性的变化是肥大细胞依赖性尚不清楚。我们通过注射P物质和某些相关肽来研究这个问题（物质P1-4，物质P4-11）进入遗传性肥大细胞缺陷的WBB 6 F1-W/Wv或WCB 6 F1-Sl/Sld小鼠、同类正常（+/+）小鼠的皮肤，和W/Wv小鼠，通过皮内注射IL-3- 1，从同源+/+小鼠的骨髓细胞体外产生的依赖性肥大细胞。当以低至2 pmol i.d.的剂量注射到正常小鼠中时，P物质诱导血管通透性显著增加和显著皮肤肿胀。P物质也诱导粒细胞浸润，尽管浸润是适度的，并且在比诱导组织肿胀所需的剂量高5倍至20倍以上的肽剂量下观察到。P物质对组织肿胀、血管通透性和粒细胞浸润的影响几乎完全依赖于肥大细胞。相比之下，P1-4物质在我们的试验中在25 nmol/部位无活性，P4-11物质诱导血管通透性适度增加，这至少部分是肥大细胞无关的。
The undecapeptide substance P is thought to mediate both vasodilatation and augmented vascular permeability when released from sensory nerve endings in the skin. Substance P also induces mast cell degranulation in vitro or in vivo. However, the extent to which substance P-induced changes in vascular permeability are mast cell-dependent is unclear. We investigated this issue by injecting substance P and certain related peptides (substance P1-4, substance P4-11) into the skin of genetically mast cell-deficient WBB6F1-W/Wv or WCB6F1-Sl/Sld mice, the congenic normal (+/+) mice, and W/Wv mice which had undergone selective local repair of their mast cell deficiency by intradermal injection of IL-3-dependent mast cells generated in vitro from the bone marrow cells of the congenic +/+ mice. Substance P induced significant augmentation of vascular permeability and significant cutaneous swelling when injected into normal mice at doses as low as 2 pmol i.d. Substance P also induced granulocyte infiltration, although the infiltrates were modest and were seen at doses of peptide from 5 to more than 20-fold higher than those required for induction of tissue swelling. The effects of substance P on tissue swelling, vascular permeability, and granulocyte infiltration were virtually entirely mast cell dependent. By contrast, substance P1-4 was inactive in our assays at 25 nmol/site, and substance P4-11 induced modest augmentation of vascular permeability, which was at least in part mast cell independent.