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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Antibiotics, Antineoplastic, Basement Membrane, Bleomycin, Chemokine CCL2, Extracellular Matrix, Humans, Intercellular Adhesion Molecule-1, Interleukin-1beta, Neutrophils, Pericytes, Transendothelial and Transepithelial Migration, Transforming Growth Factor beta1.
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Does human microvascular pericyte basement membrane remodeling regulate neutrophil recruitment? Context: Neutrophil extravasation at post-capillary venules, consisting of EC, PC, and the shared ECM, increases following fibrotic remodeling in the lung, liver, and skin. The role of fibrotic pericyte-derived ECM in regulating EC activation and neutrophil recruitment remains unexplored. To elucidate the role of human pericyte-derived ECM in EC activation, we characterized PC-derived ECM following transforming growth factor-β1, IL-1β, CCL2, or bleomycin activation, and examined surface adhesion molecule expression and neutrophil recruitment by EC cultured on PC-ECM. Pro-inflammatory activation of PC-induced deposition of compositionally distinct ECM compared with non-activated control. Bleomycin activation induced fibronectin-rich and collagen-poor ECM remodeling by PC, facilitating increased neutrophil transendothelial migration when compared with non-activated pericyte ECM (49.9 ± 3.4% versus 29.7 ± 1.4%). Increases in fibronectin compared to collagen I, are largely responsible for ECM-regulated neutrophil recruitment, as EC cultured on fibronectin supported increased neutrophil transmigration compared to collagen I (51.6 ± 6.2% versus 28.0 ± 4.8%). We attribute this difference to increased expression of ICAM-1 and its redistribution to EC borders.
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This is the first demonstration of human pericyte sensitivity to inflammatory stimuli, inducing fibrotic matrix deposition that regulates EC adhesion molecule expression and neutrophil recruitment. Final Decision: yes