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

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Abstract
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 endothclial 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 endolhelial 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‐lerminal peptide of substance P and the activation of vascular endothelial cells induced by the c‐terminal peptide of substance P.