Upregulation of the surface expression of two integrins and induction of chemotactic activity in a human leukemic cell line by Oncoimmunin-M.
Previously, it was shown that Oncoimmunin-M (OI-M), a recently identified tumor cell-derived 36 kDa protein, is able both to inhibit the proliferation of the human promyelocytic leukemic cell line HL-60 while maintaining viability in culture and to induce a bimodal distribution of CD11b, the alpha chain of the integrin MAC-1, on the cell surface (Packard, B.Z. and Komoriya, A. (1993) J. Biol. Chem. 268, 6356-6363). Now, data which reveal that exposure of HL-60 cells to this factor also brings about an increase in the mean level of surface expression of CD11c, the alpha chain of another leukocyte integrin (p150,95), but leaves CD11a, the alpha chain of the third leukointegrin (LFA-1), virtually unchanged (< 10%) are presented. Comparison of motility studies of OI-M-treated HL-60 bulk populations with control bulk populations demonstrates coinduction of CD11b and CD11c surface upregulation with chemotactic responsiveness to a gradient of the chemoattractant human C5a. Separation of motile from nonmotile cell subpopulations after exposure to C5a further reveals that individual cells which respond to this chemoattractant express increased levels of both CD11b and CD11c relative to unresponsive cells. These data correlate the upregulation of leukointegrins MAC-1 and p150,95 by a tumor cell-derived protein on a preterminally differentiated myeloid cell with chemotactic responsiveness to human C5a.
Division of Cytokine Biology, CBER, FDA, Bethesda, MD 20892.
B Z
BZ
Packard
D002460:Cell Line; D002465:Cell Movement; D002633:Chemotaxis; D015936:Complement C5a / Q000032:analysis; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D007938:Leukemia / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D015854:Up-Regulation
D016023:Integrins; D009363:Neoplasm Proteins; C088415:oncoimmunin-M; D015936:Complement C5a