NDLI: Selective down-regulation of neutrophil Mac-1 in endotoxemic hepatic microcirculation via IL-10.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Menezes, Gustavo Batista Lee, Woo-Yong Waterhouse, Christopher Curtis Matchett Zhou, Hong Kubes, Paul Cara, Denise Carmona
Description	Country affiliation: Canada Author Affiliation: Menezes GB ( Calvin, Phoebe, and Joan Snyder Institute for Infection, Immunity, and Inflammation, University of Calgary, Alberta, Canada.)
Abstract	Hepatic neutrophil adhesion during endotoxemia is an integrin-independent, CD44-dependent process. Because integrins function in other endotoxemic vasculatures, we used spinning disk confocal intravital microscopy to assess whether LPS down-modulated integrin functions in sinusoids. First, we applied fMLP onto the liver surface, and compared it with systemic LPS administration. Local fMLP caused neutrophil adhesion, crawling, and emigration for at least 2 h. Surprisingly, the number of adherent and crawling neutrophils was markedly reduced in Mac-1(-/-) and ICAM-1(-/-) mice, but not in mice treated with anti-CD44 mAb. By contrast, systemic LPS injection induced a robust accumulation of neutrophils in sinusoids, which was dependent on CD44, but not on integrins. Strikingly, local fMLP could not induce any integrin-dependent adhesion in endotoxemic mice treated with anti-CD44 mAb, indicating that Mac-1-dependent neutrophil adhesion was inhibited by LPS. This response was localized to the hepatic microvasculature because neutrophils still adhered via integrins in brain microvasculature. ICAM-1/ICAM-2 levels were not decreased, but following LPS treatment, Mac-1 was down-regulated in neutrophils localized to liver, but not in the circulation. Mac-1 down-regulation in neutrophils was not observed in IL-10(-/-) mice. In vitro neutrophil incubation with IL-10 induced direct decrease of Mac-1 expression and adhesivity in LPS-stimulated neutrophils. Therefore, our data suggest that Mac-1 is necessary for neutrophil adhesion and crawling during local inflammatory stimuli in sinusoids, but during systemic inflammation, neutrophils are exposed to high concentrations of IL-10, leading to a CD44-dependent, integrin-independent adhesion. This may be a mechanism to keep neutrophils in sinusoids for intravascular trapping.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	11
Volume Number	183
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2009-12-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Endotoxemia Immunology Interleukin-10 Liver Blood Supply Macrophage-1 Antigen Microcirculation Neutrophil Infiltration Animals Antigens, Cd44 Metabolism Brain Cell Adhesion Cell Adhesion Molecules Down-regulation Enzyme-linked Immunosorbent Assay Flow Cytometry Inflammation Lipopolysaccharides Toxicity Mice Mice, Inbred C57bl Mice, Knockout Microscopy, Confocal N-formylmethionine Leucyl-phenylalanine Analogs & Derivatives Neutrophils Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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