P-Selectin Can Support Both Th1 and Th2 Lymphocyte Rolling in the Intestinal Microvasculature

• Published in: The American journal of pathology Vol. 167; no. 6; pp. 1647 - 1660
• Main Authors: Bonder, Claudine S., Norman, M. Ursula, MacRae, Tara, Mangan, Paul R., Weaver, Casey T., Bullard, Daniel C., McCafferty, Donna-Marie, Kubes, Paul
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01-12-2005; ASIP; American Society for Investigative Pathology
• Subjects: Animals; Biological and medical sciences; Biomarkers; DNA Primers; DNA Replication; Endothelium, Vascular - cytology; Endothelium, Vascular - physiology; Gene Expression Regulation; Interleukin-10 - deficiency; Interleukin-10 - physiology; Interleukin-4 - pharmacology; Intestines - blood supply; Investigative techniques, diagnostic techniques (general aspects); Leukocyte Rolling - physiology; Medical sciences; Mice; Microcirculation - physiology; Microscopy; Neutrophil Infiltration - physiology; Original Research Paper; P-Selectin - genetics; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Polymerase Chain Reaction; RNA - isolation & purification; Th1 Cells - physiology; Th2 Cells - physiology; Tumor Necrosis Factor-alpha - pharmacology; P Selectin; Microcirculation; Anatomic pathology; Support; Digestive system; Gut; T-Lymphocyte; Cell adhesion molecule; Th1 lymphocyte; Helper cell; Th2 lymphocyte
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/S0002-9440(10)61248-5

Lymphocyte localization to inflammatory sites is paramount for developing and maintaining an immune response. Rolling is the first step in recruitment, but our knowledge of its mechanisms in Th1 and Th2 CD4
+ lymphocytes is incomplete. Whereas initial studies suggested that Th1 but not Th2 lymphocytes used P-selectin for recruitment, more recent studies have proposed that both subtypes bind selectins. We used intravital microscopy to demonstrate
in vivo
that polarized Th1 and Th2 lymphocytes both use P-selectin to roll and adhere to cytokine [tumor necrosis factor (TNF)-α or interleukin (IL)-4]-activated intestinal microvasculature. The majority of Th1 lymphocyte flux in TNF-α- and IL-4-treated animals was P-selectin-dependent. Th1 lymphocytes also interacted with E-selectin to control rolling velocity after TNF-α stimulation. Th2 lymphocytes, which make IL-4 but not interferon-γ, bound P-selectin
ex vivo
, with more than 95% rolling on P-selectin
in vivo
. Both Th1 and Th2 lymphocytes regulated rolling velocity by interacting with α
4-integrin. Furthermore, in a model of spontaneous intestinal inflammation (ie, IL-10-deficient mice), both Th1 and Th2 lymphocytes rolled, adhered, and ultimately emigrated into the local microenvironment. These results suggest that both Th1 and Th2 lymphocytes use P-selectin in the initial rolling step
in vivo
in response to a global activator of the vasculature (TNF), a subtle inducer of P-selectin (IL-4), and pathological inflammation (IL-10-deficient mice).