Immune complexes alter cerebral microvessel permeability: roles of complement and leukocyte adhesion.
Immune complexes (ICs) are potent inflammatory mediators in peripheral tissues. However, very few studies have examined the ability of ICs to induce inflammatory responses in the brain. Therefore, using preformed ICs or the reverse passive Arthus (RPA) model to localize ICs to the pial microvasculature of mice, we aimed to investigate the ability of ICs to induce an inflammatory response in the cerebral (pial) microvasculature. Application of preformed ICs immediately increased pial microvascular permeability, with a minimal change in leukocyte adhesion in pial postcapillary venules. In contrast, initiation of the RPA response in the pial microvasculature induced changes in cerebral microvascular permeability and increased leukocyte adhesion in pial postcapillary venules. The RPA response induced deposition of C3 in perivascular regions adjacent to sites of IC formation. Depletion of C3 abrogated RPA-induced microvascular permeability and leukocyte adhesion, indicating that the complement pathway was critical for this response. Inhibition of leukocyte adhesion via CD18 blockade also reduced IC-induced microvascular permeability. However, this did not require intercellular adhesion molecule-1, inasmuch as blockade of intercellular adhesion molecule-1 did not alter RPA-induced microvascular permeability and adhesion. These findings demonstrate that ICs are capable of rapidly inducing inflammatory responses in the cerebral microvasculature, with the complement pathway and leukocyte recruitment playing critical roles in microvascular dysfunction.
Department of Medicine and Monash Institute of Medical Research, Monash University, Victoria, Australia.
Karyn J
KJ
Lister
Michael J
MJ
Hickey
D000818:Animals; D000936:Antigen-Antibody Complex / Q000494:pharmacology*; D001183:Arthus Reaction / Q000276:immunology / Q000473:pathology; D002199:Capillary Permeability / Q000187:drug effects*; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism / Q000502:physiology*; D002550:Cerebral Veins / Q000502:physiology; D003176:Complement C3 / Q000502:physiology; D003165:Complement System Proteins / Q000378:metabolism / Q000502:physiology*; D042783:Endothelial Cells / Q000502:physiology; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation; D010047:Ovalbumin / Q000276:immunology
D000936:Antigen-Antibody Complex; D015815:Cell Adhesion Molecules; D003176:Complement C3; D010047:Ovalbumin; D003165:Complement System Proteins