Transendothelial migration activity of lymphokine-activated killer (LAK) cells.
With an in vitro static system using HUVEC (human umbilical vein-derived endothelial cells) cultured on type I collagen gel, we investigated the transendothelial migration activities of I1-2 activated killer (LAK) cells. Our results indicate that in comparison with unstimulated T cells, LAK cells exhibit strong transendothelial migration activity, as well as increased adhesiveness to HUVEC. Pretreatment of HUVEC for 24 h with rINF-gamma, rTNF-alpha and rIL-1 beta enhanced the LAK cell migration. The increase in the percentage of migration of LAK cells was greater than that of the percentage of adhesion but significantly less than the increase in the percentage of migration of resting T cells. The results of blocking studies using mAb strongly suggest that the enhanced migration of LAK cell was probably attributed to nonspecifically increased binding to HUVEC and markedly enhanced chemokinetic activity that was dependent primarily on the LFA-1 molecule. Among LAK cells, there were considerable differences in the migration activities of the various phenotypes. CD8+T-LAK migrated preferentially to CD4+T-LAK. CD16+ NK-LAK showed increased adhesion but somewhat decreased migration activities. However, rINF-gamma treatment of HUVEC for 24 h promoted vigorous migration of CD16+ NK-LAK, which suggests that endothelium regulate the migration of LAK cells. Based on these observations, we proposed that LAK cells, if transferred into tumor feeding vessels, can migrate into tumor tissue in considerable numbers and efficiently make contact with individual tumor cells to produce preferable clinical effects.
Kitayama
J
J
First Department of Surgery, Tokyo University, Japan.
Juji
T
T
Atomi
Y
Y
Kuroda
A
A
Muto
T
T
Kobayashi
M
M
Mitsui
Y
Y
Minami
M
M
D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D004730:Endothelium, Vascular / Q000166:cytology* / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000166:cytology* / Q000276:immunology; D017452:Receptors, IgG / Q000032:analysis; D011994:Recombinant Proteins
D017452:Receptors, IgG; D011994:Recombinant Proteins; D007371:Interferon-gamma