P-selectin glycoprotein ligand-1 contributes to wound healing predominantly as a p-selectin ligand and partly as an e-selectin ligand.
Cell adhesion molecules are critical to wound healing through leukocyte recruitment. Although P-selectin glycoprotein ligand-1 (PSGL-1) regulates leukocyte rolling by binding P-selectin, but also binding E- and L-selectins with lower affinity, little is known about a role of PSGL-1 in wound healing. To clarify a role of PSGL-1 and its interaction with E- and P-selectins in wound healing, we investigated cutaneous wound healing in PSGL-1-deficient (PSGL-1(-/-)) mice in comparison with E-selectin(-/-), P-selectin(-/-), and P-selectin(-/-) mice treated with an anti-E-selectin antibody. PSGL-1 deficiency inhibited early wound healing, which was accompanied by decreased inflammatory cell infiltration and growth factor expression. By contrast, E-selectin deficiency did not affect wound healing. In general, the inhibitory effect of PSGL-1 deficiency on wound healing was similar to that of P-selectin deficiency either alone or with E-selectin blockade. However, early granulation tissue formation, late angiogenesis, and early infiltration of neutrophils and macrophages in PSGL-1(-/-) mice were inhibited beyond the inhibition in P-selectin(-/-) mice, but to a similar level of inhibition in P-selectin(-/-) mice with E-selectin blockade. These results suggest that PSGL-1 contributes to wound healing predominantly as a P-selectin ligand and partly as an E-selectin ligand by mediating infiltration of inflammatory cells.
Tomita
Hajime
H
Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Iwata
Yohei
Y
Ogawa
Fumihide
F
Komura
Kazuhiro
K
Shimizu
Kazuhiro
K
Yoshizaki
Ayumi
A
Hara
Toshihide
T
Muroi
Eiji
E
Yanaba
Koichi
K
Bae
Sangjae
S
Takenaka
Motoi
M
Hasegawa
Minoru
M
Fujimoto
Manabu
M
Sato
Shinichi
S
D000818:Animals; D019040:E-Selectin / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008264:Macrophages / Q000502:physiology; D008407:Mast Cells / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D019007:P-Selectin / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000378:metabolism; D014945:Wound Healing
D019040:E-Selectin; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D012333:RNA, Messenger