TLR4 Accessory Molecule RP105 (CD180) Regulates Monocyte-Driven Arteriogenesis in a Murine Hind Limb Ischemia Model

Autor: J.C. Karper, A.J.N.M. Bastiaansen, Anouk Wezel, Jaap F. Hamming, Annemarie M. van Oeveren-Rietdijk, Rob C. M. de Jong, Margreet R. de Vries, Erna Peters, Anton Jan van Zonneveld, A. Yaël Nossent, Hetty C. de Boer, Sabine M.J. Welten, Paul H.A. Quax
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Physiology
Gene Expression
Hindlimb
Cardiovascular Physiology
Vascular Medicine
Monocytes
Neovascularization
Mice
White Blood Cells
Cell Movement
Ischemia
Animal Cells
Laser-Doppler Flowmetry
Medicine and Health Sciences
Antigens
Ly
Immune Response
Mice
Knockout
Innate Immune System
Multidisciplinary
medicine.anatomical_structure
Medicine
Cellular Types
medicine.symptom
Blood Flow Velocity
Research Article
medicine.medical_specialty
Science
Immune Cells
Immunology
Collateral Circulation
Neovascularization
Physiologic
Bone Marrow Cells
Spleen
Biology
Antigens
CD
Internal medicine
medicine
Animals
Vascular Diseases
Inflammation
Blood Cells
Macrophages
Monocyte
Biology and Life Sciences
Cell Biology
medicine.disease
Toll-Like Receptor 4
Disease Models
Animal
Endocrinology
Peripheral Vascular Disease
Immune System
Angiogenesis
Arteriogenesis
Bone marrow
Gene Deletion
Ex vivo
Developmental Biology
Zdroj: PLoS ONE, 9(6)
PLoS ONE
PLoS ONE, Vol 9, Iss 6, p e99882 (2014)
Popis: AimsWe investigated the role of the TLR4-accessory molecule RP105 (CD180) in post-ischemic neovascularization, i.e. arteriogenesis and angiogenesis. TLR4-mediated activation of pro-inflammatory Ly6Chi monocytes is crucial for effective neovascularization. Immunohistochemical analyses revealed that RP105+ monocytes are present in the perivascular space of remodeling collateral arterioles. As RP105 inhibits TLR4 signaling, we hypothesized that RP105 deficiency would lead to an unrestrained TLR4-mediated inflammatory response and hence to enhanced blood flow recovery after ischemia.Methods and resultsRP105-/- and wild type (WT) mice were subjected to hind limb ischemia and blood flow recovery was followed by Laser Doppler Perfusion Imaging. Surprisingly, we found that blood flow recovery was severely impaired in RP105-/- mice. Immunohistochemistry showed that arteriogenesis was reduced in these mice compared to the WT. However, both in vivo and ex vivo analyses showed that circulatory pro-arteriogenic Ly6Chi monocytes were more readily activated in RP105-/- mice. FACS analyses showed that Ly6Chi monocytes became activated and migrated to the affected muscle tissues in WT mice following induction of hind limb ischemia. Although Ly6Chi monocytes were readily activated in RP105-/- mice, migration into the ischemic tissues was hampered and instead, Ly6Chi monocytes accumulated in their storage compartments, bone marrow and spleen, in RP105-/- mice.ConclusionsRP105 deficiency results in an unrestrained inflammatory response and monocyte over-activation, most likely due to the lack of TLR4 regulation. Inappropriate, premature systemic activation of pro-inflammatory Ly6Chi monocytes results in reduced infiltration of Ly6Chi monocytes in ischemic tissues and in impaired blood flow recovery.
Databáze: OpenAIRE
Externí odkaz: