Substance P-induced augmentation of cutaneous vascular permeability and granulocyte infiltration in mice is mast cell dependent.
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/W or WCB6F1- SI/SId mice the congenic normal (+/+) mice, and W/W 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 infiltrate 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.
Yano
H
H
Department of Pathology, Beth Israel Hospital, Boston, Massachusetts 02215.
Wershil
B K
BK
Arizono
N
N
Galli
S J
SJ
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D005337:Fibrin / Q000378:metabolism; D006098:Granulocytes / Q000187:drug effects*; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D013373:Substance P / Q000494:pharmacology*
D013373:Substance P; D005337:Fibrin