Human Dermal Endothelial Cells Express Membrane-Associated Mast Cell Growth Factor

Abstract

Mast cell growth factor (MGF), a molecule that serves as a ligand for the receptor tyrosine kinase c-kit, is important in mast cell differentiation, migration, and activation. Previous studies of paraffin-embedded human skin using antibody to murine MGF and reverse transcription-polymerase chain reaction have demonstrated MGF protein and mRNA expression in keratinocytes and isolated dermal cells. We utilized a monoclonal antibody to human MGF to further define patterns of immunoreactivity in frozen specimens of neonatal and adult skin from normal individuals and from patients with urticaria pigmentosa. In addition to keratinocytes and isolated dermal cells in normal and urticaria pigmentosa skin, MGF was detected in cells lining superficial and mid-dermal vessels. Co-expression of MGF and the vascular antigen CD31, and immunoelectron microscopy, identified MGF-positive cells as endothelial cells. Patterns of endothelial MGF expression were not influenced by mast cell degranulation and endothelial E-selectin induction in vitro. By ultrastructure, unfixed specimens demonstrated MGF expression both within the endothelial cytoplasm and in association with lumenal, but not ablumenal, surfaces. Specimens fixed with Nakane's solution had diminished endothelial cytoplasmic MGF reactivity, but lumenal expression was maintained, suggesting persistence of a membrane-associated reactivity. MGF mRNA was also detected in cultured dermal microvascular endothelial cells using reverse transcription-polymerase chain reaction. These data establish human dermal endothelial cells as sites of MGF production and expression in human skin. Mast cell precursors must home to skin via vascular channels and differentiate in the immediate perivascular space. Thus, endothelial MGF may be an important determinant of adhesion and differentiation of mast cell progenitors expressing receptors for MGF.

Stem Cell Factor Combined with Matrix Proteins Regulates the Attachment and Migration of Melanocyte Precursors of Human Hair Follicles <i>in Vitro</i>

“…28,29) Previous studies suggested that SCF/ KIT signaling is involved in the mechanism of melanocyte migration, such as melanocyte migration from the neural crest into the epidermis, 30) melanocyte distribution in the hair follicle during fetal development, 31) melanocyte migration in chemotherapy-induced hair loss 32) and increased migration of melanocytes into the epidermis caused by local SCF injection. 33) In vitro, SCF stimulates epidermal melanocyte chemokinesis and increases the speed of melanocyte movement on FN-coated dishes, 21,34) but the effect of SCF on MPs migration was unknown.…”

Mast cells and their mediators in cutaneous wound healing – active participants or innocent bystanders?

“…In the skin, SCF is synthesized by fibroblasts, keratinocytes, Langerhans cells, mast cells and endothelial cells (79,155). SCF promotes the survival, proliferation, differentiation and maturation of mast cells, and it induces and/or enhances their mediator release, chemotaxis, adhesion and migration (10,(155)(156)(157).…”

Genetic evidence for convergence of c-Kit– and α4 integrin–mediated signals on class IA PI-3kinase and the Rac pathway in regulating integrin-directed migration in mast cells

“…54 Activation of integrins by cytokines, such as SCF, can result in enhanced binding of integrins to their cognate ligands, and these changes contribute to an integrated signal for coordinated cellular events such as directed cell migration. Since SCF is expressed by endothelial cells, 55,56 it is likely to cooperate with integrins in modulating biologic responses in circulating mast cells. This was recently illustrated by means of a coculture system in which proliferation of mast cells was shown to be dependent on the cooperation between c-Kit and ␣ 4 ␤ 1 integrins on mast cells and VCAM-1 and SCF on HUVEC cells.…”