PMID- 25299318
OWN - NLM
STAT- MEDLINE
DCOM- 20151228
LR  - 20231110
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 10
DP  - 2014
TI  - Contribution of corneal neovascularization to dendritic cell migration into the 
      central area during human corneal infection.
PG  - e109859
LID - 10.1371/journal.pone.0109859 [doi]
LID - e109859
AB  - Compared with the peripheral corneal limbus, the human central cornea lacks blood 
      vessels, which is responsible for its immunologically privileged status and high 
      transparency. Dendritic cells (DCs) are present in the central avascular area of 
      inflamed corneas, but the mechanisms of their migration to this location are 
      poorly understood. Here, we investigated the contribution of vessel formation to 
      DC migration into the central cornea, and analyzed the DC chemotactic factors 
      produced by human corneal epithelial (HCE) cells. Using human eyes obtained from 
      surgical procedures, we then assessed vessel formation, DC distribution, and 
      activin A expression immunohistochemically. The results demonstrated increased 
      numbers of vessels and DCs in the central area of inflamed corneas, and a 
      positive correlation between the number of vessels and DCs. Activin A was 
      expressed in the subepithelial space and the endothelium of newly formed blood 
      vessels in the inflamed cornea. In infected corneas, DCs were present in the 
      central area but no vascularization was observed, suggesting the presence of 
      chemotactic factors that induced DC migration from the limbal vessels. To test 
      this hypothesis, we assessed the migration of monocyte-derived DCs toward HCE 
      cell supernatants with or without lipopolysaccharide (LPS) stimulation of HCE 
      cells and inflammatory cytokines (released by HCE cells). DCs migrated toward 
      tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, and activin A, as well 
      as LPS-stimulated HCE cell supernatants. The supernatant contained elevated 
      TNF-alpha, IL-6, and activin A levels, suggesting that they were produced by HCE 
      cells after LPS stimulation. Therefore, vessels in the central cornea might 
      constitute a DC migration route, and activin A expressed in the endothelium of 
      newly formed vessels might contribute to corneal vascularization. Activin A also 
      functions as a chemotactic factor, similar to HCE-produced TNF-alpha and IL-6. These 
      findings enhance our understanding of the pathophysiology of corneal inflammation 
      during infection.
FAU - Narumi, Mari
AU  - Narumi M
AD  - Department of Ophthalmology and Visual Sciences, Yamagata University Faculty of 
      Medicine, Yamagata, Japan.
FAU - Kashiwagi, Yoshiko
AU  - Kashiwagi Y
AD  - Department of Health and Nutrition, Yamagata Prefectural Yonezawa Women's Junior 
      College, Yamagata, Japan.
FAU - Namba, Hiroyuki
AU  - Namba H
AD  - Department of Ophthalmology and Visual Sciences, Yamagata University Faculty of 
      Medicine, Yamagata, Japan.
FAU - Ohe, Rintaro
AU  - Ohe R
AD  - Department of Pathological Diagnostics, Yamagata University Faculty of Medicine, 
      Yamagata, Japan.
FAU - Yamakawa, Mitsunori
AU  - Yamakawa M
AD  - Department of Pathological Diagnostics, Yamagata University Faculty of Medicine, 
      Yamagata, Japan.
FAU - Yamashita, Hidetoshi
AU  - Yamashita H
AD  - Department of Ophthalmology and Visual Sciences, Yamagata University Faculty of 
      Medicine, Yamagata, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141009
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (IL6 protein, human)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (activin A)
RN  - 104625-48-1 (Activins)
SB  - IM
MH  - Activins/biosynthesis/metabolism
MH  - Animals
MH  - Cell Movement/drug effects/genetics
MH  - Cornea/drug effects/pathology
MH  - Corneal Neovascularization/*genetics/pathology
MH  - Dendritic Cells/*pathology
MH  - Epithelium, Corneal/metabolism/pathology
MH  - Gene Expression/drug effects/genetics
MH  - Humans
MH  - Interleukin-6/biosynthesis/genetics
MH  - Keratitis/*genetics/pathology
MH  - Limbus Corneae/pathology
MH  - Lipopolysaccharides/toxicity
MH  - Mice
MH  - *Neovascularization, Pathologic
PMC - PMC4192358
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/10/10 06:00
MHDA- 2015/12/29 06:00
PMCR- 2014/10/09
CRDT- 2014/10/10 06:00
PHST- 2014/03/19 00:00 [received]
PHST- 2014/09/14 00:00 [accepted]
PHST- 2014/10/10 06:00 [entrez]
PHST- 2014/10/10 06:00 [pubmed]
PHST- 2015/12/29 06:00 [medline]
PHST- 2014/10/09 00:00 [pmc-release]
AID - PONE-D-14-05809 [pii]
AID - 10.1371/journal.pone.0109859 [doi]
PST - epublish
SO  - PLoS One. 2014 Oct 9;9(10):e109859. doi: 10.1371/journal.pone.0109859. 
      eCollection 2014.