Anti-LFA-1 blocking antibodies prevent mobilization of hematopoietic progenitor cells induced by interleukin-8

J F Pruijt, Y van Kooyk, C G Figdor, I J Lindley, R Willemze, W E Fibbe

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Previously, we have shown that interleukin (IL)-8 induces the rapid (15 to 30 minutes) mobilization of hematopoietic progenitor cells (HPC) in mice. Because integrins are essential for adhesion and transendothelial migration of HPC, we studied the involvement of the beta2-integrin leukocyte function-associated antigen-1 (LFA-1) in IL-8-induced mobilization. After a single injection of blocking anti-LFA-1 antibodies, no mobilization of colony-forming cells was observed. In addition, when mice were pretreated with anti-LFA-1 or saline and subsequently injected with 30 microg of IL-8, mobilization of HPC was completely blocked. We showed that this was not due to anti-LFA-1 antibodies affecting colony formation, as addition of anti-LFA-1 antibodies to colony cultures in semisolid medium had no inhibitory activity. Also, anti-intercellular adhesion molecule (ICAM)-1 antibodies, directed to the main ligand of LFA-1 significantly inhibited the IL-8-induced mobilization. Furthermore, IL-1-induced mobilization was significantly inhibited by anti-LFA-1 antibodies. Because LFA-1 is reported to be expressed on more differentiated HPC, it was considered that the IL-8-induced mobilization of more primitive HPC would not be blocked by anti-LFA-1 antibodies. Transplantation of blood-derived mononuclear cells (MNC) from IL-8-mobilized animals pretreated with anti-LFA-1 antibodies protected only 25% of lethally irradiated recipient mice, whereas the radioprotection rate of control mice transplanted with MNC derived from IL-8-mobilized animals was 86% (P < .01). Anti-LFA-1 antibodies did not interfere with stem cell homing, as transplantation of IL-8-mobilized blood MNC, incubated in vitro with these antibodies resulted in 100% radioprotection. We conclude that anti-LFA-1 antibodies completely prevent the rapid mobilization of colony-forming cells and of cells with radioprotective capacity induced by IL-8. These results indicate a major role for the beta2-integrin LFA-1 in the IL-8-induced mobilization of hematopoietic stem cells.

Original languageEnglish
Pages (from-to)4099-105
Number of pages7
JournalBlood
Volume91
Issue number11
Publication statusPublished - 1 Jun 1998

Cite this

Pruijt, J. F., van Kooyk, Y., Figdor, C. G., Lindley, I. J., Willemze, R., & Fibbe, W. E. (1998). Anti-LFA-1 blocking antibodies prevent mobilization of hematopoietic progenitor cells induced by interleukin-8. Blood, 91(11), 4099-105.
Pruijt, J F ; van Kooyk, Y ; Figdor, C G ; Lindley, I J ; Willemze, R ; Fibbe, W E. / Anti-LFA-1 blocking antibodies prevent mobilization of hematopoietic progenitor cells induced by interleukin-8. In: Blood. 1998 ; Vol. 91, No. 11. pp. 4099-105.
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title = "Anti-LFA-1 blocking antibodies prevent mobilization of hematopoietic progenitor cells induced by interleukin-8",
abstract = "Previously, we have shown that interleukin (IL)-8 induces the rapid (15 to 30 minutes) mobilization of hematopoietic progenitor cells (HPC) in mice. Because integrins are essential for adhesion and transendothelial migration of HPC, we studied the involvement of the beta2-integrin leukocyte function-associated antigen-1 (LFA-1) in IL-8-induced mobilization. After a single injection of blocking anti-LFA-1 antibodies, no mobilization of colony-forming cells was observed. In addition, when mice were pretreated with anti-LFA-1 or saline and subsequently injected with 30 microg of IL-8, mobilization of HPC was completely blocked. We showed that this was not due to anti-LFA-1 antibodies affecting colony formation, as addition of anti-LFA-1 antibodies to colony cultures in semisolid medium had no inhibitory activity. Also, anti-intercellular adhesion molecule (ICAM)-1 antibodies, directed to the main ligand of LFA-1 significantly inhibited the IL-8-induced mobilization. Furthermore, IL-1-induced mobilization was significantly inhibited by anti-LFA-1 antibodies. Because LFA-1 is reported to be expressed on more differentiated HPC, it was considered that the IL-8-induced mobilization of more primitive HPC would not be blocked by anti-LFA-1 antibodies. Transplantation of blood-derived mononuclear cells (MNC) from IL-8-mobilized animals pretreated with anti-LFA-1 antibodies protected only 25{\%} of lethally irradiated recipient mice, whereas the radioprotection rate of control mice transplanted with MNC derived from IL-8-mobilized animals was 86{\%} (P < .01). Anti-LFA-1 antibodies did not interfere with stem cell homing, as transplantation of IL-8-mobilized blood MNC, incubated in vitro with these antibodies resulted in 100{\%} radioprotection. We conclude that anti-LFA-1 antibodies completely prevent the rapid mobilization of colony-forming cells and of cells with radioprotective capacity induced by IL-8. These results indicate a major role for the beta2-integrin LFA-1 in the IL-8-induced mobilization of hematopoietic stem cells.",
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author = "Pruijt, {J F} and {van Kooyk}, Y and Figdor, {C G} and Lindley, {I J} and R Willemze and Fibbe, {W E}",
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Pruijt, JF, van Kooyk, Y, Figdor, CG, Lindley, IJ, Willemze, R & Fibbe, WE 1998, 'Anti-LFA-1 blocking antibodies prevent mobilization of hematopoietic progenitor cells induced by interleukin-8' Blood, vol. 91, no. 11, pp. 4099-105.

Anti-LFA-1 blocking antibodies prevent mobilization of hematopoietic progenitor cells induced by interleukin-8. / Pruijt, J F; van Kooyk, Y; Figdor, C G; Lindley, I J; Willemze, R; Fibbe, W E.

In: Blood, Vol. 91, No. 11, 01.06.1998, p. 4099-105.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Anti-LFA-1 blocking antibodies prevent mobilization of hematopoietic progenitor cells induced by interleukin-8

AU - Pruijt, J F

AU - van Kooyk, Y

AU - Figdor, C G

AU - Lindley, I J

AU - Willemze, R

AU - Fibbe, W E

PY - 1998/6/1

Y1 - 1998/6/1

N2 - Previously, we have shown that interleukin (IL)-8 induces the rapid (15 to 30 minutes) mobilization of hematopoietic progenitor cells (HPC) in mice. Because integrins are essential for adhesion and transendothelial migration of HPC, we studied the involvement of the beta2-integrin leukocyte function-associated antigen-1 (LFA-1) in IL-8-induced mobilization. After a single injection of blocking anti-LFA-1 antibodies, no mobilization of colony-forming cells was observed. In addition, when mice were pretreated with anti-LFA-1 or saline and subsequently injected with 30 microg of IL-8, mobilization of HPC was completely blocked. We showed that this was not due to anti-LFA-1 antibodies affecting colony formation, as addition of anti-LFA-1 antibodies to colony cultures in semisolid medium had no inhibitory activity. Also, anti-intercellular adhesion molecule (ICAM)-1 antibodies, directed to the main ligand of LFA-1 significantly inhibited the IL-8-induced mobilization. Furthermore, IL-1-induced mobilization was significantly inhibited by anti-LFA-1 antibodies. Because LFA-1 is reported to be expressed on more differentiated HPC, it was considered that the IL-8-induced mobilization of more primitive HPC would not be blocked by anti-LFA-1 antibodies. Transplantation of blood-derived mononuclear cells (MNC) from IL-8-mobilized animals pretreated with anti-LFA-1 antibodies protected only 25% of lethally irradiated recipient mice, whereas the radioprotection rate of control mice transplanted with MNC derived from IL-8-mobilized animals was 86% (P < .01). Anti-LFA-1 antibodies did not interfere with stem cell homing, as transplantation of IL-8-mobilized blood MNC, incubated in vitro with these antibodies resulted in 100% radioprotection. We conclude that anti-LFA-1 antibodies completely prevent the rapid mobilization of colony-forming cells and of cells with radioprotective capacity induced by IL-8. These results indicate a major role for the beta2-integrin LFA-1 in the IL-8-induced mobilization of hematopoietic stem cells.

AB - Previously, we have shown that interleukin (IL)-8 induces the rapid (15 to 30 minutes) mobilization of hematopoietic progenitor cells (HPC) in mice. Because integrins are essential for adhesion and transendothelial migration of HPC, we studied the involvement of the beta2-integrin leukocyte function-associated antigen-1 (LFA-1) in IL-8-induced mobilization. After a single injection of blocking anti-LFA-1 antibodies, no mobilization of colony-forming cells was observed. In addition, when mice were pretreated with anti-LFA-1 or saline and subsequently injected with 30 microg of IL-8, mobilization of HPC was completely blocked. We showed that this was not due to anti-LFA-1 antibodies affecting colony formation, as addition of anti-LFA-1 antibodies to colony cultures in semisolid medium had no inhibitory activity. Also, anti-intercellular adhesion molecule (ICAM)-1 antibodies, directed to the main ligand of LFA-1 significantly inhibited the IL-8-induced mobilization. Furthermore, IL-1-induced mobilization was significantly inhibited by anti-LFA-1 antibodies. Because LFA-1 is reported to be expressed on more differentiated HPC, it was considered that the IL-8-induced mobilization of more primitive HPC would not be blocked by anti-LFA-1 antibodies. Transplantation of blood-derived mononuclear cells (MNC) from IL-8-mobilized animals pretreated with anti-LFA-1 antibodies protected only 25% of lethally irradiated recipient mice, whereas the radioprotection rate of control mice transplanted with MNC derived from IL-8-mobilized animals was 86% (P < .01). Anti-LFA-1 antibodies did not interfere with stem cell homing, as transplantation of IL-8-mobilized blood MNC, incubated in vitro with these antibodies resulted in 100% radioprotection. We conclude that anti-LFA-1 antibodies completely prevent the rapid mobilization of colony-forming cells and of cells with radioprotective capacity induced by IL-8. These results indicate a major role for the beta2-integrin LFA-1 in the IL-8-induced mobilization of hematopoietic stem cells.

KW - Animals

KW - Antibodies/pharmacology

KW - Blood Cell Count

KW - Colony-Forming Units Assay

KW - Hematopoietic Stem Cell Mobilization

KW - Hematopoietic Stem Cells/drug effects

KW - Integrin alpha4beta1

KW - Integrins/immunology

KW - Intercellular Adhesion Molecule-1/immunology

KW - Interleukin-8/pharmacology

KW - Lymphocyte Function-Associated Antigen-1/immunology

KW - Mice

KW - Mice, Inbred BALB C

KW - Monocytes/transplantation

KW - Receptors, Lymphocyte Homing/immunology

KW - Whole-Body Irradiation

M3 - Article

VL - 91

SP - 4099

EP - 4105

JO - Blood

JF - Blood

SN - 0006-4971

IS - 11

ER -

Pruijt JF, van Kooyk Y, Figdor CG, Lindley IJ, Willemze R, Fibbe WE. Anti-LFA-1 blocking antibodies prevent mobilization of hematopoietic progenitor cells induced by interleukin-8. Blood. 1998 Jun 1;91(11):4099-105.