Critical but divergent roles for CD62L and CD44 in directing blood monocyte trafficking in vivo during inflammation

Abstract

Using noninvasive in vivo imaging and experimental autoimmune uveoretinitis as a model, we show for the first time that the mechanisms controlling blood monocyte recirculation through peripheral and lymphoid tissues alter during inflammation. The recirculation of monocytes in mice with ocular inflammation but not controls was found to depend on the selectin CD62-ligand (CD62L) and on CD44. Not only was rolling efficiency ablated or markedly reduced in antibody-treated mice, but most of the labeled monocytes also disappeared from the circulation within seconds, anti-CD44–treated monocytes homing to the lymph nodes and anti–CD62L-treated monocytes homing to the spleen. Our data indicate that, although PSGL-1 has a partial role in the transmigration of monocytes into the inflamed retina, CD62L has a key role in regulating recruitment of monocytes to lymphoid tissue from the blood during inflammation and that CD44 is required to maintain CD62L+ inflammatory monocytes within the circulation during inflammation. This effect was systemic, because sequestered monocytes accumulated in mesenteric as well as draining cervical lymph nodes, and inflammation dependent, because depletion of circulating blood monocytes was much reduced or absent in normal mice and accumulations of adoptively transferred monocytes in the lymphoid tissues did not occur.

CD44 Antibody Inhibition of Macrophage Phagocytosis Targets Fcγ Receptor– and Complement Receptor 3–Dependent Mechanisms

“…Moreover, IM7 also directly inhibits CR3-mediated RBC phagocytosis but did not affect dectin-1- mediated phagocytosis of zymosan. These findings suggest that in addition to its previously reported inhibitory effects on phagocytic cell infiltration into inflammatory sites (27), IM7 is able to selectively inhibit two different opsonic phagocytic mechanisms in macrophages.…”

“…Abs to CD44 have been successfully used in the treatment of several animal models of autoimmune and inflammatory diseases, including experimental autoimmune encephalomyelitis (18,19), collagen-or Ab-induced arthritis (7,(20)(21)(22)(23), autoimmune diabetes (24,25), experimental autoimmune uveoretinitis (26,27), experimental colitis (28), experimental pulmonary eosinophilia (29), and cutaneous delayed-type hypersensitivity (30). The mAb rat anti-human/mouse CD44, IM7, which recognizes an extracellular epitope on the CD44s, has been extensively used in many of these studies, and robust anti-inflammatory effects have been reported with the administration of the Ab in these disease models (7,18,19,21,22,(24)(25)(26).…”

Myosin 1g regulates cytoskeleton plasticity, cell migration, exocytosis, and endocytosis in B lymphocytes

“…The Myo1g −/− B lymphocytes were slower and developed shorter trajectories upon stimulation with an agonist chemokine, CXCL13. Again, this behavior could be attributed to the reduced expression of adhesion molecules, which are involved in homing/recirculation processes in lymphocytes [46,47]. As previously mentioned, the reduction of the membrane tension exerted by class I myosin deficiency likely impairs the polarization of the migrating B cells toward a chemokine gradient, thus slowing down their movement.…”

Citrus hallabong [(Citrus unshiu × C. sinensis) × C. reticulata)] exerts potent anti-inflammatory properties in murine splenocytes and TPA-induced murine ear oedema model

“…CD62L regulates the homing of blood monocytes to lymphoid tissues (Xu et al 2008) and mediates the infiltration of leukocytes to the site of inflammation (Tedder et al 1995). CD44 þ cells are responsible for maintaining the CD62L þ inflammatory monocytes' circulation during inflammation (Xu et al 2008) and leukocytes' infiltration to site of inflammation (Sarraj et al 2006). According to Xu et al (2008), the obstruction of the CD44/CD62L þ cells can contribute to the reduction of inflammatory response caused by leukocytes and monocytes.…”

“…CD44 þ cells are responsible for maintaining the CD62L þ inflammatory monocytes' circulation during inflammation (Xu et al 2008) and leukocytes' infiltration to site of inflammation (Sarraj et al 2006). According to Xu et al (2008), the obstruction of the CD44/CD62L þ cells can contribute to the reduction of inflammatory response caused by leukocytes and monocytes. Therefore, HE's anti-inflammatory activity is also presented by decreasing the CD44/CD62L þ memory T-cells.…”