Platelet-activating factor causes goblet cell depletion in the conjunctiva.
Platelet-activating factor (PAF) (1-O-hexadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine) produced dose-dependent depletion of the goblet cell population associated with the conjunctival epithelium. Reductions in goblet cell numbers did not correspond to leukocyte infiltration and were consistent with a direct effect of PAF. In contrast, LTD4 and LTE4 did not affect the goblet cell population although they caused massive eosinophil infiltration into the conjunctival epithelium. Histamine also produced conjunctival goblet cell depletion, but this appeared secondary to eosinophil degranulation and resultant epithelial desquamation. In addition to goblet cell expulsion, PAF produced an increase in conjunctival microvascular permeability over an identical dose-range. PAF-induced leukocyte emigration was small or absent and comprised a neutrophil infiltrate which exhibited no clear dose-dependent relationship. Lyso-PAF produced effects only at the highest dose employed where pathological changes and a distinct increase in conjunctival microvascular permeability were evident. Lyso-PAF- and PAF-induced increases in conjunctival microvascular permeability were virtually abolished by the PAF antagonist CV-6209. The pronounced inhibitory activity of CV-6209 suggests that high doses of lyso-PAF may either weakly stimulate conjunctival PAF receptors or that there may be sufficient conversion of lyso-PAF to biologically active levels of PAF.
Woodward
D F
DF
Allergan, Inc., Discovery Research, Irvine, CA 92715.
Spada
C S
CS
Nieves
A L
AL
Hawley
S B
SB
Williams
L S
LS
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D003228:Conjunctiva / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects; D017999:Leukotriene E4; D008297:Male; D009504:Neutrophils / Q000187:drug effects; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000494:pharmacology; D013189:SRS-A / Q000494:pharmacology
D010972:Platelet Activating Factor; D011726:Pyridinium Compounds; D013189:SRS-A; C053321:CV 6209; D017999:Leukotriene E4; D006632:Histamine