TY - JOUR
T1 - P-selectin glycoprotein ligand-1 contributes to wound healing predominantly as a P-selectin ligand and Partly as an E-selectin ligand
AU - Tomita, Hajime
AU - Iwata, Yohei
AU - Ogawa, Fumihide
AU - Komura, Kazuhiro
AU - Shimizu, Kazuhiro
AU - Yoshizaki, Ayumi
AU - Hara, Toshihide
AU - Muroi, Eiji
AU - Yanaba, Koichi
AU - Bae, Sangjae
AU - Takenaka, Motoi
AU - Hasegawa, Minoru
AU - Fujimoto, Manabu
AU - Sato, Shinichi
N1 - Funding Information:
We thank Ms Y Yamada, M Matsubara, A Usui, M Yozaki, and K Shimoda for technical assistance. This work was supported by a grant of Research on Intractable Diseases from the Ministry of Health, Labour and Welfare of Japan.
PY - 2009/8
Y1 - 2009/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=67651119769&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67651119769&partnerID=8YFLogxK
U2 - 10.1038/jid.2008.446
DO - 10.1038/jid.2008.446
M3 - Article
C2 - 19177138
AN - SCOPUS:67651119769
VL - 129
SP - 2059
EP - 2067
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 8
ER -