Substance P-induced augmentation of cutaneous vascular permeability and granulocyte infiltration in mice is mast cell dependent.

Abstract

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 P,I4, substance P4.11) into the skin of genetically mast cell-deficient WBB6F,-W/W' or WCB6F1-SI/Sid mice, the congenic normal (+/+) mice, and WIW' 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 P-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.

Tissue-dependent differences in the asynchronous appearance of mast cells in normal mice and in congenic mast cell-deficient mice after infusion of normal bone marrow cells

“…W = W v mice contains far fewer mast cells than the same tissue in = mice. On the other hand, in certain types of locally contained inflammation, such as passive cutaneous anaphylaxis [16] and dermal application of phorbol myristate acetate (PMA) [17] or substance P [18], local mast cells in BM …”

Augmentation of reverse arthus reaction by mast cells in mice.

“…Galli and Kitamura have published a comprehensive discussion ofthe value of mast cell-deficient mice for the investigation of the role of mast cells in biological responses (2). Galli and his co-workers have shown the importance of mast cells in the expression of such inflammatory processes as leukocyte infiltration, edema, and fibrin deposition in cutaneous anaphylaxis, and after application of phorbol myristate acetate and substance P (3)(4)(5). At the same time we initiated studies investigating the role of mast cells in inflammation other than immediate hypersensitivity.…”

Lack of significant skin inflammation during elimination by apoptosis of large numbers of mouse cutaneous mast cells after cessation of treatment with stem cell factor

“…[9][10][11][12][13] Such responses include cutaneous contact hypersensitivity reactions, 9 IgE-dependent passive cutaneous anaphylaxis responses 10 and reactions to the intradermal injection of substance P 11 or SCF 12 or the epicutaneous application of PMA. 13 For example, in tests of cutaneous contact hypersensitivity reactions, the 125 I-fibrin deposition assay was more sensitive than standard measurements of tissue swelling in detecting weak responses.…”