Cytotoxicity of human eosinophil granule major basic protein to human nasal sinus mucosa in vitro.
The toxic effects of the human eosinophil granule major basic protein (MBP), reduced and alkylated, were studied on human nasal mucosa in vitro. With a microscope coupled with a television monitor (magnification x 2500) and videotape recorder, we investigated the effects of MBP on the mucosa and the ciliary activity of single cells. In nasal mucosal specimens from normal individuals, MBP, 5 mumol/L and 10 mumol/L, significantly inhibited (p less than 0.01) ciliary activity by 4 and 1 hours of exposure, respectively. At these same MBP concentrations, the mucosal surface profiles were altered by 4 hours of exposure, and ciliostasis was 75% to 100% complete by 9 and 6 hours, respectively. In a mucosal specimen from a patient with nasal allergy, 1 mumol/L of MBP significantly inhibited (p less than 0.01) ciliary activity by 1 hour; alteration of the mucosal surface profile appeared by 3 hours of exposure, and ciliostasis was 75% to 100% by 13 hours. Similar alterations of the mucosal surface profile were observed with specimens from a second patient with allergies; in contrast, 1 mumol/L of MPB had no effect on specimens from a nonallergic patient. These results indicate that MBP damages human upper respiratory epithelium, causing ciliostasis and alteration of the epithelial surface at concentrations likely achieved in vivo. Furthermore, the mucosal specimens from two allergic patients were damaged by concentrations of MBP that had no effect on mucosal specimens from a normal individual.
Hisamatsu
K
K
Department of Otorhinolaryngology, Yamanashi College of Medicine, Tamaho, Japan.
Ganbo
T
T
Nakazawa
T
T
Murakami
Y
Y
Gleich
G J
GJ
Makiyama
K
K
Koyama
H
H
D001798:Blood Proteins / Q000302:isolation & purification / Q000633:toxicity*; D002923:Cilia / Q000187:drug effects / Q000473:pathology; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000378:metabolism*; D005005:Ethmoid Sinus / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D008443:Maxillary Sinus / Q000187:drug effects* / Q000473:pathology; D009297:Nasal Mucosa / Q000187:drug effects* / Q000473:pathology; D012130:Respiratory Hypersensitivity / Q000473:pathology; D012260:Ribonucleases
D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D012260:Ribonucleases