OBJECTIVE: Immune complex-induced responses involve multiple cellular and molecular mechanisms. However, how these pathways interact in the initiation of immune complex-induced response is poorly understood. Therefore the aim of this study was to investigate the immediate response of the microvasculature to immune complex formation. METHODS: The reverse passive Arthus (RPA) model was applied to the mouse cremaster muscle. Intravital microscopy was used to examine alterations in florescein isothiocyanate (FITC)-dextran leakage from microvessels, and endothelial interactions of leukocytes and platelets in postcapillary venules. RESULTS: Immune complex deposition induced rapid increases in microvascular permeability and leukocyte adhesion and emigration. Inhibition of platelet-activating factor (PAF) and leukotrienes inhibited the increase in permeability. Depletion of C3 reduced immune complex-mediated leukocyte recruitment and permeability, and a similar effect on permeability was observed following inhibition of leukocyte adhesion. Mast cell stabilization reduced increases in leukocyte adhesion and emigration but accelerated the increase in microvascular permeability. Platelet-endothelial interactions also increased during the RPA response, and platelet depletion delayed the changes in permeability and inhibited leukocyte recruitment. CONCLUSIONS: This study demonstrates that immune complexes induce a rapid induction of complement-dependent leukocyte recruitment, and neutrophil-dependent microvascular dysfunction. Furthermore, this study identifies a role for platelets in promoting immune complex-induced leukocyte recruitment.
OBJECTIVE: Immune complex-induced responses involve multiple cellular and molecular mechanisms. However, how these pathways interact in the initiation of immune complex-induced response is poorly understood. Therefore the aim of this study was to investigate the immediate response of the microvasculature to immune complex formation. METHODS: The reverse passive Arthus (RPA) model was applied to the mouse cremaster muscle. Intravital microscopy was used to examine alterations in florescein isothiocyanate (FITC)-dextran leakage from microvessels, and endothelial interactions of leukocytes and platelets in postcapillary venules. RESULTS: Immune complex deposition induced rapid increases in microvascular permeability and leukocyte adhesion and emigration. Inhibition of platelet-activating factor (PAF) and leukotrienes inhibited the increase in permeability. Depletion of C3 reduced immune complex-mediated leukocyte recruitment and permeability, and a similar effect on permeability was observed following inhibition of leukocyte adhesion. Mast cell stabilization reduced increases in leukocyte adhesion and emigration but accelerated the increase in microvascular permeability. Platelet-endothelial interactions also increased during the RPA response, and platelet depletion delayed the changes in permeability and inhibited leukocyte recruitment. CONCLUSIONS: This study demonstrates that immune complexes induce a rapid induction of complement-dependent leukocyte recruitment, and neutrophil-dependent microvascular dysfunction. Furthermore, this study identifies a role for platelets in promoting immune complex-induced leukocyte recruitment.
Authors: Mitchell J Cohen; Michel Carles; Karim Brohi; Carolyn S Calfee; Pamela Rahn; Mariah S Call; Brian B Chesebro; Michael A West; Jean-François Pittet Journal: J Trauma Date: 2010-06
Authors: Emily R Elliott; Jessica A Van Ziffle; Patrizia Scapini; Brandon M Sullivan; Richard M Locksley; Clifford A Lowell Journal: J Immunol Date: 2011-09-14 Impact factor: 5.422