Platelet-activating factor stimulates lung pericyte growth in vitro

Area of Science:

• Pulmonary Hypertension Research
• Cell Biology
• Vascular Medicine

Background:

• Platelet-activating factor (PAF) is implicated in inflammatory conditions such as sepsis and acute lung injury.
• Pulmonary hypertension, often seen in these conditions, involves microvasculature muscularization driven by pericyte proliferation.
• PAF is hypothesized to mediate this pericyte proliferation and subsequent vascular remodeling.

Purpose of the Study:

• To investigate the direct effects of Platelet-activating factor (PAF) on the in vitro growth of rat lung pericytes.
• To determine if PAF acts as a cytokine influencing pericyte proliferation in the context of pulmonary vascular disease.

Main Methods:

• Cultured rat lung pericytes were exposed to varying concentrations of semisynthetic and synthetic PAF (16:0 and 18:0).
• Pericyte growth was assessed over 7 days in media with and without serum.
• DNA synthesis was measured via [3H]thymidine incorporation.
• The role of the PAF receptor was evaluated using the specific blocker CV-3988.
• Apoptosis was assessed to rule out cytotoxic effects.

Main Results:

• Semisynthetic PAF significantly stimulated pericyte proliferation (29-31%) compared to controls, both in proliferating and growth-arrested cells.
• PAF exposure increased [3H]thymidine incorporation by 79%, indicating enhanced DNA synthesis.
• Synthetic 16:0 PAF promoted growth, while 18:0 PAF did not.
• The PAF-receptor blocker CV-3988 abolished the growth-promoting effects of PAF.
• PAF did not induce apoptosis in the cultured pericytes.

Conclusions:

• Platelet-activating factor (PAF) directly stimulates lung pericyte growth in vitro.
• These findings suggest PAF may function as a cytokine, contributing to the muscularization of pulmonary vessel walls.
• PAF's role in pericyte proliferation could be a key mechanism in the development of pulmonary hypertension during inflammatory lung diseases.