Nerve growth factor and eosinophils in inflamed juvenile conjunctival nevus.
OBJECTIVE
To study both systemic and ocular nerve growth factor (NGF) in inflamed juvenile conjunctival nevus (IJCN), a benign, inflammatory juxtalimbal lesion characterized by many intralesional eosinophils, and to investigate the behavior of eosinophils cocultured on lesional and extralesional fibroblasts obtained from IJCN biopsies, in relation to NGF.


METHODS
Eight patients with IJCN (7-15 years old) and six with noninflamed conjunctival compound nevus (12-30 years old) participated in the study. Conjunctival biopsy specimens were used for routine histology, immunohistochemistry (NGF, trkA, eosinophil cationic protein, and tryptase determination), in situ hybridization (NGF mRNA), and determination of fibroblast growth. Blood of patients with IJCN was used to measure NGF levels (by ELISA) and to isolate eosinophils (magnet activated cell sorter [MACS]). Eosinophils were seeded on lesional and extralesional fibroblasts and their adherence, survival (by trypan blue staining), and functional activity (by eosinophil peroxidase [EPO] assay) were assessed after 4 days.


RESULTS
NGF in the blood of patients with IJCN and eosinophils and mast cells in their conjunctivas, were significantly elevated. NGF protein, NGF mRNA, and trkA were found to be increased in IJCN biopsy specimens compared with noninflamed compound nevi. Some NGF and trkA colocalized with eosinophils and mast cells. Lesional fibroblasts produced high amounts of NGF in comparison with extralesional fibroblasts and significantly enhanced eosinophil adherence, without influencing either their viability or activation. Adherence and EPO release were increased, in both lesional and extralesional fibroblasts.


CONCLUSIONS
The triggering factors that lead to the prominent inflammation in IJCN are unknown. The data in the current study, showing the presence of increased NG-trkA, eosinophils, and mast cells in IJCN and the modulation of eosinophil properties by lesional fibroblasts partly through NGF, suggest a possible association between IJCN and allergic inflammation. Alternatively, this process may represent a direct immune response induced by the nevus itself.
Levi-Schaffer
Francesca
F
Department of Pharmacology and the David R. Bloom Center for Pharmacy School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel. fls@cc.huji.ac.il
Micera
Alessandra
A
Zamir
Ehud
E
Mechoulam
Hadas
H
Puxeddu
Ilaria
I
Piliponsky
Adrian M
AM
Aloe
Luigi
L
Pe'er
Jacob
J
D000293:Adolescent; D000328:Adult; D001798:Blood Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002648:Child; D018920:Coculture Techniques; D003230:Conjunctival Neoplasms / Q000378:metabolism* / Q000473:pathology; D003231:Conjunctivitis / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts; D006801:Humans; D007124:Immunoenzyme Techniques; D007073:Immunoglobulin E / Q000097:blood; D017403:In Situ Hybridization; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D009506:Nevus / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D020917:Receptor, trkA; D012260:Ribonucleases; D012697:Serine Endopeptidases / Q000378:metabolism; D053802:Tryptases
D001798:Blood Proteins; D002352:Carrier Proteins; D047091:Eosinophil Granule Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D007073:Immunoglobulin E; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D012260:Ribonucleases; D012697:Serine Endopeptidases; D053802:Tryptases