Histamine effects on conjunctival fibroblasts from patients with vernal conjunctivitis

Histamine, an important mast cell mediator in allergic disorders, may affec t extracellular matrix production and cell growth in vernal keratoconjuncti vitis (VKC), In the present study, the histamine reactivity of conjunctival fibroblasts derived from VKC patients was investigated in vitro, Conjuncti val fibroblast cultures were derived from biopses of 8 tarsal VKC patients and 5 normal subjects. These cells were maintained in vitro and stimulated with different concentrations of histamine with and without H1 (clorphenira mine) and H2 (cimetidine) receptor antagonists, Comparisons were made to fi broblasts grown in the same media without histamine and to fibroblasts stim ulated with just antihistamine. The effects of histamine were evaluated by: (1) the MTT test to assess cell proliferation; (2) an in vitro wound model for cell migration and (3) the measurement of procollagen I (PIP) and proc ollagen III (PIIIP) in supernatants for collagen production. Results showed : (1) While VKC-derived fibroblasts proliferated at a faster rate than norm al cells in unstimulated media, after histamine stimulation, VKC and normal cells grew at a similar rate. Both H1 and H2 antagonists significantly inh ibited (P < 0.05) histamine-induced cell proliferation. (2) Histamine enhan ced cell migration after wounding; this effect was inhibited only by H2 ant agonism. (3) When stimulated with histamine, VKC fibroblasts produced signi ficantly more PIP than those in control media. Furthermore, VKC-derived fib roblasts were more sensitive to histamine challenge, producing significantl y more PIP than normal fibroblasts. H1 and H2 antagonists did not modify hi stamine-stimulated PIP production. The enhanced proliferative and productiv e capacity of VKC fibroblasts may be the result of a selective overgrowth o f one or more fibroblast subpopulations in a chronically inflamed tissue. H istamine increased proliferation, migration and collagen production in both normal and VKC fibroblasts. Since H2 antagonism modulated both cell growth and migration, but not histamine-induced collagen production, the latter m ay be mediated by a different receptor. These results showed that histamine is at least partially responsible for fibroblast stimulation. (C) 1999 Aca demic Press.