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Title: Human macrophage differentiation involves an interaction between integrins and fibronectin

The authors have examined the role of integrins and extracellular matrix (ECM) proteins in macrophage differentiation of (1) human HL-60 myeloid leukemia cells induced by phorbol 12-myristate 13-acetate (PMA) and (2) human peripheral blood monocytes induced by either PMA or macrophage-colony stimulating factor (M-CSF). Increased {beta}{sub 1} integrin and fibronectin (FN) gene expression was observed in PMA-treated HL-60 cells and PMA- or M-CSF-treated monocytes, even at a time preceding the manifestation of macrophage markers. Treated HL-60 cells and monocytes also released and deposited FN on the culture dishes. An HL-60 cell variant, HL-525, which is deficient in protein kinase C {beta} (PKC{beta}) and resistant to PMA-induced differentiation, failed to express FN after PMA treatment. Restoration of PKC{beta} resulted in PMA-induced FN gene expression and macrophage differentiation. The macrophage phenotype induced in HL-60 cells or monocytes was attenuated by anti-{beta}{sub 1} integrin or anti-FN MAbs. The authors suggest that macrophage differentiation involves activation of PKC and expression of specific integrins and ECM proteins. The stimulated cells, through their integrins, attach and spread on these substrates by binding to the deposited ECM proteins. This attachment and spreading in turn, through integrin signaling, leads to the macrophage phenotype.
Authors:
; ; ;
Publication Date:
OSTI Identifier:
515532
Report Number(s):
ANL/CMB/PP-92848
ON: DE97008258; TRN: AHC29718%%47
DOE Contract Number:
W-31109-ENG-38
Resource Type:
Technical Report
Resource Relation:
Other Information: PBD: 14 Mar 1997
Research Org:
Argonne National Lab., IL (United States)
Sponsoring Org:
USDOE Office of Energy Research, Washington, DC (United States)
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; CELL DIFFERENTIATION; MACROPHAGES; BIOCHEMICAL REACTION KINETICS; MAN; PROTEINS; PHORBOL ESTERS; GENE REGULATION; EXPERIMENTAL DATA; PHENOTYPE; GROWTH FACTORS