Neuropeptide regulation of human dermal microvascular endothelial cell ICAM-1 expression and function.
There is increasing evidence that sensory nerves may participate in cutaneous inflammatory responses by the release of neuropeptides such as substance P (SP). We examined the direct effect of SP on human dermal microvascular endothelial cell (HDMEC) intercellular adhesion molecule 1 (ICAM-1) expression and function. Our results indicated that, although cultured HDMEC expressed mRNA for neurokinin receptors 1, 2, and 3 (NK-1R, NK-2R, and NK-3R), SP initiated a rapid increase in HDMEC intracellular Ca2+ levels, primarily by the activation of NK-1R. Immunohistochemistry studies likewise demonstrated that HDMEC predominantly expressed NK-1R. The addition of SP to HDMEC resulted in a rapid increase in cellular ICAM-1 mRNA levels, followed by a fivefold increase in ICAM-1 cell surface expression. This functionally resulted in a threefold increase in 51Cr-labeled binding of J-Y lymphoblastoid cells to HDMEC. In vivo studies demonstrated a marked increase in microvascular ICAM-1 immunostaining 24 and 48 h after application of capsaicin to the skin. These results indicate that neuropeptides such as SP are capable of directly activating HDMEC to express increased levels of functional ICAM-1 and further support the role of the cutaneous neurological system in modulating inflammatory processes in the skin.
Quinlan
K L
KL
Department of Dermatology and Emory Skin Diseases Research Core Center, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Song
I S
IS
Bunnett
N W
NW
Letran
E
E
Steinhoff
M
M
Harten
B
B
Olerud
J E
JE
Armstrong
C A
CA
Wright Caughman
S
S
Ansel
J C
JC
D002211:Capsaicin / Q000494:pharmacology; D002448:Cell Adhesion / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D016922:Cellular Senescence / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology; D008833:Microcirculation / Q000502:physiology; D009479:Neuropeptides / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D018039:Receptors, Tachykinin / Q000235:genetics; D012867:Skin / Q000098:blood supply* / Q000187:drug effects; D013373:Substance P / Q000494:pharmacology
D009479:Neuropeptides; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D018039:Receptors, Tachykinin; D018799:Intercellular Adhesion Molecule-1; D013373:Substance P; D002211:Capsaicin