Substance P-induced granulocyte infiltration in mouse skin: the mast cell-dependent granulocyte infiltration by the N-terminal peptide is enhanced by the activation of vascular endothelial cells by the C-terminal peptide.
Previous studies have shown that substance P induces granulocyte infiltration in mouse skin, which is mediated through mast cell degranulation. However, it is not yet known whether the direct effect of substance P on vascular endothelial cells is involved in the granulocyte infiltration in the skin. To solve this issue, we used the N-terminal peptide substance P1-9 (SP1-9), which is active for mast cells but inactive for vascular endothelial cells, and the C-terminal peptide SP6-11, which is active for vascular endothelial cells but inactive for mast cells, since substance P activates both mast cells and vascular endothelial cells. The subcutaneous administration of substance P (10(-7)-10(-5)M) caused granulocyte (neutrophil and eosinophil) infiltration in the skin of BALB/c mice 6 h after the injection. SP1-9 (10(-5)-10(-4) M) also caused granulocyte infiltration of mouse skin which was associated with mast cell degranulation. In contrast, SP6-11 (10(-7)-10(-4) M), which was found to increase the vascular permeability of endothelial cells in mouse skin, induced no significant granulocyte infiltration nor mast cell degranulation. However, SP6-11 (10(-5)-10(-4) M) enhanced SP1-9-induced granulocyte infiltration in the skin without any significant increase in mast cell degranulation. We conclude that substance P causes granulocyte infiltration in mouse skin through both mast cell degranulation induced by the N-terminal peptide of substance P and the activation of vascular endothelial cells induced by the C-terminal peptide of substance P.
Iwamoto
I
I
Second Department of Internal Medicine, Chiba University School of Medicine, Japan.
Tomoe
S
S
Tomioka
H
H
Yoshida
S
S
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects; D006098:Granulocytes / Q000502:physiology*; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000494:pharmacology; D012867:Skin / Q000166:cytology; D013329:Structure-Activity Relationship; D013373:Substance P / Q000737:chemistry / Q000494:pharmacology*
D010446:Peptide Fragments; D013373:Substance P