Fractalkine Preferentially Mediates Arrest and Migration of CD16+ Monocytes

CD16+ monocytes represent 5–10% of peripheral blood monocytes in normal individuals and are dramatically expanded in several pathological conditions including sepsis, human immunodeficiency virus 1 infection, and cancer. CD16+ monocytes produce high levels of proinflammatory cytokines and may represent dendritic cell precursors in vivo. The mechanisms that mediate the recruitment of CD16+ monocytes into tissues remain unknown. Here we investigate molecular mechanisms of CD16+ monocyte trafficking and show that migration of CD16+ and CD16− monocytes is mediated by distinct combinations of adhesion molecules and chemokine receptors. In contrast to CD16− monocytes, CD16+ monocytes expressed high CX3CR1 and CXCR4 but low CCR2 and CD62L levels and underwent efficient transendo-thelial migration in response to fractalkine (FKN; FKN/CX3CL1) and stromal-derived factor 1α (CXCL12) but not monocyte chemoattractant protein 1 (CCL2). CD16+ monocytes arrested on cell surface–expressed FKN under flow with higher frequency compared with CD16− monocytes. These results demonstrate that FKN preferentially mediates arrest and migration of CD16+ monocytes and suggest that recruitment of this proinflammatory monocyte subset to vessel walls via the CX3CR1-FKN pathway may contribute to vascular and tissue injury during pathological conditions.

[1]  P. Debré,et al.  Decreased Atherosclerotic Lesion Formation in CX3CR1/Apolipoprotein E Double Knockout Mice , 2003, Circulation.

[2]  I. Charo,et al.  Decreased atherosclerosis in CX3CR1-/- mice reveals a role for fractalkine in atherogenesis. , 2003, The Journal of clinical investigation.

[3]  K. Schäkel,et al.  The CD16+ (FcγRIII+) Subset of Human Monocytes Preferentially Becomes Migratory Dendritic Cells in a Model Tissue Setting , 2002, The Journal of experimental medicine.

[4]  E. Masliah,et al.  Expression of stromal cell-derived factor 1α protein in HIV encephalitis , 2002, Journal of Neuroimmunology.

[5]  P. Kubes.  Introduction: The complexities of leukocyte recruitment , 2002 .

[6]  T. Espevik,et al.  The Proinflammatory CD14+CD16+DR++ Monocytes Are a Major Source of TNF1 , 2002, The Journal of Immunology.

[7]  Eric J Kunkel,et al.  Chemokines and the tissue-specific migration of lymphocytes. , 2002, Immunity.

[8]  F. Luscinskas,et al.  Reduced expression of junctional adhesion molecule and platelet/endothelial cell adhesion molecule-1 (CD31) at human vascular endothelial junctions by cytokines tumor necrosis factor-alpha plus interferon-gamma Does not reduce leukocyte transmigration under flow. , 2001, The American journal of pathology.

[9]  Steffen Jung,et al.  Inflammatory Chemokine Transport and Presentation in HEV , 2001, The Journal of experimental medicine.

[10]  J. Sedgwick,et al.  Tumor Necrosis Factor–dependent Segmental Control of MIG Expression by High Endothelial Venules in Inflamed Lymph Nodes Regulates Monocyte Recruitment , 2001, The Journal of experimental medicine.

[11]  W. Muller.  New Mechanisms and Pathways for Monocyte Recruitment , 2001, The Journal of experimental medicine.

[12]  T. Imai,et al.  Fractalkine and vascular injury. , 2001, Trends in immunology.

[13]  I. Kurth,et al.  Monocyte Selectivity and Tissue Localization Suggests a Role for Breast and Kidney–Expressed Chemokine (Brak) in Macrophage Development , 2001, The Journal of experimental medicine.

[14]  F. Luscinskas,et al.  Wall shear stress: the missing step for T cell transmigration? , 2001, Nature Immunology.

[15]  S. Lira,et al.  Generation and Analysis of Mice Lacking the Chemokine Fractalkine , 2001, Molecular and Cellular Biology.

[16]  G. Jansen,et al.  Enhanced expression of fractalkine in HIV-1 associated dementia , 2001, Journal of Neuroimmunology.

[17]  M. Ernst,et al.  Heterogeneity of human peripheral blood monocyte subsets , 2001, Journal of leukocyte biology.

[18]  M. Mack,et al.  Selective mobilization of CD14(+)CD16(+) monocytes by exercise. , 2000, American journal of physiology. Cell physiology.

[19]  A. Sher,et al.  Analysis of Fractalkine Receptor CX3CR1 Function by Targeted Deletion and Green Fluorescent Protein Reporter Gene Insertion , 2000, Molecular and Cellular Biology.

[20]  C. Weber,et al.  Differential chemokine receptor expression and function in human monocyte subpopulations , 2000, Journal of leukocyte biology.

[21]  B. Chandran,et al.  Long-Term Infection and Transformation of Dermal Microvascular Endothelial Cells by Human Herpesvirus 8 , 1999, Journal of Virology.

[22]  D. Patel,et al.  Fractalkine and CX3CR1 Mediate a Novel Mechanism of Leukocyte Capture, Firm Adhesion, and Activation under Physiologic Flow , 1998, The Journal of experimental medicine.

[23]  T. Schall,et al.  Identification and Molecular Characterization of Fractalkine Receptor CX3CR1, which Mediates Both Leukocyte Migration and Adhesion , 1997, Cell.

[24]  M. McGrath,et al.  Unique monocyte subset in patients with AIDS dementia , 1997, The Lancet.

[25]  Wei Wang,et al.  A new class of membrane-bound chemokine with a CX3C motif , 1997, Nature.

[26]  H. Ziegler-Heitbrock,et al.  Heterogeneity of human blood monocytes: the CD14+ CD16+ subpopulation. , 1996, Immunology today.

[27]  F. Luscinskas,et al.  L- and P-selectins, but not CD49d (VLA-4) integrins, mediate monocyte initial attachment to TNF-alpha-activated vascular endothelium under flow in vitro. , 1996, Journal of immunology.

[28]  C. Estcourt,et al.  CD14lowCD16high: A cytokine‐producing monocyte subset which expands during human immunodeficiency virus infection , 1995, European journal of immunology.

[29]  B. Perussia,et al.  FcγRIII (CD16) on human macrophages is a functional product of the FcγRIII‐2 gene , 1991 .

[30]  E. Butcher,et al.  Identification of a human peripheral lymph node homing receptor: a rapidly down-regulated adhesion molecule. , 1990, Proceedings of the National Academy of Sciences of the United States of America.