Interleukin-11 enhancement of VLA-5 mediated adhesion of CD34+ cells from cord blood to fibronectin is associated with the PI-3 kinase pathway.
Adhesion is required for cell growth, differentiation, survival, and function. Cell adhesion is mediated by a structurally diverse group of plasma membrane receptors, each exhibiting specialized ligand-binding properties that are needed for specific tasks. Integrin-mediated adhesion is important for hematopoietic stem (HSC)/progenitor (HPC) cell survival and may prevent programmed cell death. Interleukin (IL)-11, a multi-functional cytokine secreted by the bone marrow environment, plays an important role in regulating growth and differentiation of HSCs/HPCs. In this report, we demonstrate that IL-11 enhanced adhesion of freshly isolated and 3 day-expanded CD34+ cells to immobilized fibronectin. the expression of very late antigen (VLA)-4 and VLA-5 integrins was detected on CD34+ cells. CD34+ cells also expressed a-chain and gp130 subunits of the IL-11 receptor (R). Enhanced adhesion by IL-11 was mediated via activation of VLA-5 integrins, since this action could be blocked by monoclonal antibodies against beta 1 and alpha 5, but not alpha 4, integrins. Addition of phosphatidylinositol (PI)-3 kinase inhibitors blocked IL-11 enhanced adhesion of CD34+ cells to fibronectin. The results suggest that this enhanced adhesion is associated with the PI-3 kinase pathway, an inside-out signaling pathway.
Wang
L S
LS
Department of Microbiology/Immunology, Indiana University School of Medicine, Indianapolis 46202-5254, USA.
Liu
H J
HJ
Broxmeyer
H E
HE
Lu
L
L
D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018952:Antigens, CD34 / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D007231:Infant, Newborn; D039041:Integrin alpha4beta1; D016023:Integrins / Q000378:metabolism; D017370:Interleukin-11 / Q000494:pharmacology*; D053703:Interleukin-11 Receptor alpha Subunit; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012313:RNA / Q000032:analysis; D017469:Receptors, Fibronectin / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000378:metabolism; D053702:Receptors, Interleukin-11; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D016029:Receptors, Very Late Antigen / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D018952:Antigens, CD34; D017931:DNA Primers; D005353:Fibronectins; D039041:Integrin alpha4beta1; D016023:Integrins; D017370:Interleukin-11; D053703:Interleukin-11 Receptor alpha Subunit; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012313:RNA; D017469:Receptors, Fibronectin; D018123:Receptors, Interleukin; D053702:Receptors, Interleukin-11; D016201:Receptors, Lymphocyte Homing; D016029:Receptors, Very Late Antigen; C508428:IL11RA protein, human