Effect of histamine on proliferation of normal human adult lung fibroblasts.

Abstract

Fibrotic lung tissue shows increased connective tissue deposition and fibroblast proliferation and in addition a substantial increase in mast cell numbers in and around the fibrotic area. To elucidate the question ofwhether products of mast cells affect the proliferative behaviour of structural cells in the lung and thereby contribute to fibrogenesis, the effect of histamine, a prominent mast cell derived mediator, on the in vitro proliferation of primary cultures of normal adult human lung fibroblasts was studied. Histamine enhanced fibroblast proliferation in a dose dependent manner, with an optimum effect at a physiological concentration of 10 -' mol/l. This effect occurred when cells were exposed to histamine at restricted times during cell growth and was shown to depend in part on the stage of the cell cycle reached by the fibroblasts. The histamine induced proliferation was mediated through an H2 histamine receptor on the fibroblast, being inhibited by cimetidine, an H, antagonist, and not by pyrilamine maleate, an antagonist of the H, receptor. Mast cell products such as histamine may interact with and promote the increased fibroblast proliferation found in pulmonary fibrosis.

Inhibition of Proteasome Activity Induces Formation of Alternative Proteasome Complexes

“…Primary Cell Culture-Primary human lung fibroblasts (phLF) were isolated from organ donor lungs and cultured as previously described (37)(38)(39). 24 h prior to treatment phLF were synchronized by incubation in starvation medium containing 1% FBS.…”

Mast Cells: A Pivotal Role in Pulmonary Fibrosis

“…Agents targeting the inflammatory macrophages, neutrophils, and lymphocytes have not halted pathologic fibrosis. The increased numbers of mast cells associated with pulmonary fibrosis is well documented, as they also contribute to the inflammatory response but their role is unclear (Kawanami et al, 1979;Jordana et al, 1988). Clinically, a correlation between mast cells and fibrosis is recognized, but a causal relationship linking mast cells and fibroblasts to fibrogenesis has yet to be demonstrated (Metcalfe et al, 1997).…”

“…We previously reported that lung mast cells synthesize and release renin, which triggers local ANG II formation (Silver et al, 2004;Veerappan et al, 2008). Histamine, another mast cell mediator, may also contribute to fibrosis by stimulating fibroblast proliferation ( Jordana et al, 1988).…”

Regulation of Activin A Expression in Mast Cells and Asthma: Its Effect on the Proliferation of Human Airway Smooth Muscle Cells

“…MC promote migration and proliferation of fibroblasts by releasing proinflammatory mediators and growth factors (16,17). For example, MC tryptase is able to activate and induce proliferation of fibroblasts (18).…”